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Imaging-guided cancer treatment


Imaging-guided cancer treatment

Writer & reporter: Dror Nir, PhD

It is estimated that the medical imaging market will exceed $30 billion in 2014 (FierceMedicalImaging). To put this amount in perspective; the global pharmaceutical market size for the same year is expected to be ~$1 trillion (IMS) while the global health care spending as a percentage of Gross Domestic Product (GDP) will average 10.5% globally in 2014 (Deloitte); it will reach ~$3 trillion in the USA.

Recent technology-advances, mainly miniaturization and improvement in electronic-processing components is driving increased introduction of innovative medical-imaging devices into critical nodes of major-diseases’ management pathways. Consequently, in contrast to it’s very small contribution to global health costs, medical imaging bears outstanding potential to reduce the future growth in spending on major segments in this market mainly: Drugs development and regulation (e.g. companion diagnostics and imaging surrogate markers); Disease management (e.g. non-invasive diagnosis, guided treatment and non-invasive follow-ups); and Monitoring aging-population (e.g. Imaging-based domestic sensors).

In; The Role of Medical Imaging in Personalized Medicine I discussed in length the role medical imaging assumes in drugs development.  Integrating imaging into drug development processes, specifically at the early stages of drug discovery, as well as for monitoring drug delivery and the response of targeted processes to the therapy is a growing trend. A nice (and short) review highlighting the processes, opportunities, and challenges of medical imaging in new drug development is: Medical imaging in new drug clinical development.

The following is dedicated to the role of imaging in guiding treatment.

Precise treatment is a major pillar of modern medicine. An important aspect to enable accurate administration of treatment is complementing the accurate identification of the organ location that needs to be treated with a system and methods that ensure application of treatment only, or mainly to, that location. Imaging is off-course, a major component in such composite systems. Amongst the available solution, functional-imaging modalities are gaining traction. Specifically, molecular imaging (e.g. PET, MRS) allows the visual representation, characterization, and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In oncology, it can be used to depict the abnormal molecules as well as the aberrant interactions of altered molecules on which cancers depend. Being able to detect such fundamental finger-prints of cancer is key to improved matching between drugs-based treatment and disease. Moreover, imaging-based quantified monitoring of changes in tumor metabolism and its microenvironment could provide real-time non-invasive tool to predict the evolution and progression of primary tumors, as well as the development of tumor metastases.

A recent review-paper: Image-guided interventional therapy for cancer with radiotherapeutic nanoparticles nicely illustrates the role of imaging in treatment guidance through a comprehensive discussion of; Image-guided radiotherapeutic using intravenous nanoparticles for the delivery of localized radiation to solid cancer tumors.

 Graphical abstract

 Abstract

One of the major limitations of current cancer therapy is the inability to deliver tumoricidal agents throughout the entire tumor mass using traditional intravenous administration. Nanoparticles carrying beta-emitting therapeutic radionuclides [DN: radioactive isotops that emits electrons as part of the decay process a list of β-emitting radionuclides used in radiotherapeutic nanoparticle preparation is given in table1 of this paper.) that are delivered using advanced image-guidance have significant potential to improve solid tumor therapy. The use of image-guidance in combination with nanoparticle carriers can improve the delivery of localized radiation to tumors. Nanoparticles labeled with certain beta-emitting radionuclides are intrinsically theranostic agents that can provide information regarding distribution and regional dosimetry within the tumor and the body. Image-guided thermal therapy results in increased uptake of intravenous nanoparticles within tumors, improving therapy. In addition, nanoparticles are ideal carriers for direct intratumoral infusion of beta-emitting radionuclides by convection enhanced delivery, permitting the delivery of localized therapeutic radiation without the requirement of the radionuclide exiting from the nanoparticle. With this approach, very high doses of radiation can be delivered to solid tumors while sparing normal organs. Recent technological developments in image-guidance, convection enhanced delivery and newly developed nanoparticles carrying beta-emitting radionuclides will be reviewed. Examples will be shown describing how this new approach has promise for the treatment of brain, head and neck, and other types of solid tumors.

The challenges this review discusses

  • intravenously administered drugs are inhibited in their intratumoral penetration by high interstitial pressures which prevent diffusion of drugs from the blood circulation into the tumor tissue [1–5].
  • relatively rapid clearance of intravenously administered drugs from the blood circulation by kidneys and liver.
  • drugs that do reach the solid tumor by diffusion are inhomogeneously distributed at the micro-scale – This cannot be overcome by simply administering larger systemic doses as toxicity to normal organs is generally the dose limiting factor.
  • even nanoparticulate drugs have poor penetration from the vascular compartment into the tumor and the nanoparticles that do penetrate are most often heterogeneously distributed

How imaging could mitigate the above mentioned challenges

  • The inclusion of an imaging probe during drug development can aid in determining the clearance kinetics and tissue distribution of the drug non-invasively. Such probe can also be used to determine the likelihood of the drug reaching the tumor and to what extent.

Note: Drugs that have increased accumulation within the targeted site are likely to be more effective as compared with others. In that respect, Nanoparticle-based drugs have an additional advantage over free drugs with their potential to be multifunctional carriers capable of carrying both therapeutic and diagnostic imaging probes (theranostic) in the same nanocarrier. These multifunctional nanoparticles can serve as theranostic agents and facilitate personalized treatment planning.

  • Imaging can also be used for localization of the tumor to improve the placement of a catheter or external device within tumors to cause cell death through thermal ablation or oxidative stress secondary to reactive oxygen species.

See the example of Vintfolide in The Role of Medical Imaging in Personalized Medicine

vinta

Note: Image guided thermal ablation methods include radiofrequency (RF) ablation, microwave ablation or high intensity focused ultrasound (HIFU). Photodynamic therapy methods using external light devices to activate photosensitizing agents can also be used to treat superficial tumors or deeper tumors when used with endoscopic catheters.

  • Quality control during and post treatment

For example: The use of high intensity focused ultrasound (HIFU) combined with nanoparticle therapeutics: HIFU is applied to improve drug delivery and to trigger drug release from nanoparticles. Gas-bubbles are playing the role of the drug’s nano-carrier. These are used both to increase the drug transport into the cell and as ultrasound-imaging contrast material. The ultrasound is also used for processes of drug-release and ablation.

 HIFU

Additional example; Multifunctional nanoparticles for tracking CED (convection enhanced delivery)  distribution within tumors: Nanoparticle that could serve as a carrier not only for the therapeutic radionuclides but simultaneously also for a therapeutic drug and 4 different types of imaging contrast agents including an MRI contrast agent, PET and SPECT nuclear diagnostic imaging agents and optical contrast agents as shown below. The ability to perform multiple types of imaging on the same nanoparticles will allow studies investigating the distribution and retention of nanoparticles initially in vivo using non-invasive imaging and later at the histological level using optical imaging.

 multi

Conclusions

Image-guided radiotherapeutic nanoparticles have significant potential for solid tumor cancer therapy. The current success of this therapy in animals is most likely due to the improved accumulation, retention and dispersion of nanoparticles within solid tumor following image-guided therapies as well as the micro-field of the β-particle which reduces the requirement of perfectly homogeneous tumor coverage. It is also possible that the intratumoral distribution of nanoparticles may benefit from their uptake by intratumoral macrophages although more research is required to determine the importance of this aspect of intratumoral radionuclide nanoparticle therapy. This new approach to cancer therapy is a fertile ground for many new technological developments as well as for new understandings in the basic biology of cancer therapy. The clinical success of this approach will depend on progress in many areas of interdisciplinary research including imaging technology, nanoparticle technology, computer and robot assisted image-guided application of therapies, radiation physics and oncology. Close collaboration of a wide variety of scientists and physicians including chemists, nanotechnologists, drug delivery experts, radiation physicists, robotics and software experts, toxicologists, surgeons, imaging physicians, and oncologists will best facilitate the implementation of this novel approach to the treatment of cancer in the clinical environment. Image-guided nanoparticle therapies including those with β-emission radionuclide nanoparticles have excellent promise to significantly impact clinical cancer therapy and advance the field of drug delivery.

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Pacemakers, Implantable Cardioverter Defibrillators (ICD) and Cardiac Resynchronization Therapy (CRT)

Curators: Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

Updated on 2/16/2015

Mild, non-ischemic heart failure might be more deadly than thought, an Austrian group found, calling for broader ICD use.

SOURCE

http://www.medpagetoday.com/Cardiology/Strokes/50048?isalert=1&uun=g99985d3527R5099207u&utm_source=breaking-news&utm_medium=email&utm_campaign=breaking-news&xid=NL_breakingnews_2015-02-16

 

The voice of our Series A Content Consultant: Justin D Pearlman, MD, PhD, FACC

Pacemakers place one or more wires into heart muscle to trigger electro-mechanically coupled contraction. A single wire to the right atrium is called an AAI pacemaker (atrial sensing, atrial triggering, inhibit triggering if sensed). A single wire to the right ventricle is called a VVI pacemaker (ventricular sensing, ventricular triggering, inhibit if sensed). With two wires to the heart more combinations are possible, including atrial-ventricular sequential activation, a closer mimic to normal function (DDDR pacemaker: dual sensing, dual triggering, dual functions, and rate-responsive to mimic exercise adjustment of heart rate). Three wires are used for synchronization: one to the right atrium, one to the right ventricle apex, and a third lead into a distal branch of the coronary sinus to activate the far side of the left ventricle. Resynchronization is used to compensate for a dilated ventricle, especially one with conduction delays, where the timing of activation is so unbalanced that the heart contraction approaches a wobbling motion rather than a well coordinated contraction. Adjusting timing of activation of the right ventricle and left ventricle can offset dysynchrony (unbalanced timing) and thereby increase the amount of blood ejected by each heart beat contraction (ejection fraction). Patients with dilated cardiomyopathy and significant conduction delays can improve the ejection fraction by 10 or more percentage points, which offers a significant improvement in exertion tolerance and heart failure symptoms.

Patients with ejection fraction below 35%, among others, have an elevated risk of life-ending arrhythmias such as ventricular tachycardia. Ventricular tachycardia is an extreme example of a wobbling heart in which the electrical activation sequence circles around the heart sequentially activating a portion and blocking its ability to respond until the electric signal comes around again. Whenever a portion of the heart is activated, ions shift location, and further activation of that region is not possible until sufficient time passes so that the compartmentalized ion concentrations can be restored (repolarization). Pacing can interrupt ventricular tachycardia by depolarizing a region that supported the circular activation pattern. Failing that, an electric shock can stop an ineffective rhythm. After all regions stop activation, they will generally reactivate in the normal pulsatile synchronous manner. An implanted cardiac defibrillator is a device designed to apply an internal electric shock to pause all activation and thereby interrupt ventricular tachycardia.
UPDATED on 12/31/2013

Published on Friday, 27 December 2013

S-ICD – Subcutaneous Implantable Cardioverter Defibrillator – Boston Scientific

Boston Scientific Subcutaneous Implantable Cardiodefibrillator Device S-ICD

S-ICD – Subcutaneous Implantable Cardioverter Defibrillator – Boston Scientific

Boston Scientific Subcutaneous Implantable Cardiodefibrillator Device S-ICD

‘Regular’ Pacemaker/ICD with Leads and a ‘Can’
When we think of Pacemakers and ICD’s we naturally think of a ‘Can’ and Leads that track down into the heart. Whilst these devices work fantastically well and will continue to do so. Unfortunately the ‘lead’ part of the device opens the door for a few complications to possibly arise. Those who have a Pacemaker or ICD will probably be familiar with concerns over;
  1. Systemic Infection – Infections travelling down the Leads into the Heart
  2. Lead Displacement – The Lead moving away from the heart tissue and thus becoming pretty useless.
  3. Vascular/Organ Injury – Damage to the blood vessels being used for access or perforation of heart wall.
  4. Pneumothorax (damage to the lining around the Lung), Haemothorax (build up of blood in the chest cavity), and air embolism (air bubble trapped in a blood vessel).
These complications are one of the key motivations behind developing ‘leadless’ devices the first of which the St Jude Nanostim, a small VVI Pacemaker that fits directly into the heart.
Another device to address these issues is the Boston Scientific S-ICD

What is the Boston Scientific S-ICD?

The S-ICD is what is sometimes referred to as a ‘shock box’ it does not have the pacemaker functionality that many other ICD’s do have. It is ONLY there to terminate dangerous Arrhythmias.
*It does not have the pacing functionality of traditional ICD‘s because it DOES NOT HAVE A LEAD THAT ENTERS THE HEART.*
It is not a Pacemaker!
 
Without the lead(s) ENTERING the heart via a blood vessel there is a reduction in the risks mentioned previously that are associated traditional device. Another of the benefits is that the S-ICD is positioned and implanted using anatomical landmarks (visible parts of your body) and not Fluoroscopy (video X-Ray) which reduces radiation exposure to the patient.

Positioning of the S-ICD.

Boston Scientific Subcutaneous Implantable Cardiodefibrillator Device S-ICD

The ‘Can‘ (metal box that contains all the circuitry and battery), is buried under the skin on the outside of the ribs. Put your arms down by your sides, the device would go where your ribs meet the middle of your bicep. A lead is then run under the skin to the centre of your chest where its is anchored and then north, under the skin again until the tip of the lead is roughly at the top of the sternum.
For you physicians out there the ‘can’ is positioned at the mid-axillary line between the 5th and 6th intercostal spaces, the lead is then tunnelled to a small Xiphoid incision and then tunnelled north to a superior incision.

How is an S-ICD Implanted?

VIEW VIDEO
Having spoken to Boston Scientific it is becoming more apparent that the superior incision (cut at the top of the chest) may actually be removed from the procedure guidance as simply tunnelling the lead and ‘wedging’ the tip at that point is satisfactory – THIS IS NOT CONFIRMED AT THE MOMENT AND IS THEREFORE NOT PROCEDURE ADVICE.
Boston Scientific Subcutaneous Implantable Cardiodefibrillator Device S-ICD
Image Courtesy of
http://www.bostonscientific.com/

How does the S-ICD Work?

A ‘Shock Box’ basically needs to do 2 things. Firstly be able to SENSE if the heart has entered a Dangerous Arrhythmia and Secondly, be able to treat it.
The treatment part of the functionality is the easy bit – it delivers an electric shock across a ‘circuit’ that involves a large amount of the tissue in the heart. The lead has two ‘electrodes’ and the ‘Can’ is a third electrode allowing you different shocking ‘vectors’. By vectors we mean directions and area through which the electricity travels during a shock. This gives us extra options when implanting a device as some vectors will work better than others for the treatment of dangerous arrhythmias.

Shocking Vectors?

This is a concept you are familiar with without even thinking about it… when you are watching ER or another TV program and they Defibrillate the patient using the metal paddles, where do they position them? One either side of the heart? Precisely!! this is creating a ‘vector’ across the heart to involve the cardiac tissue. The paddles would be a lot less effective if you put one on the knee and one on the foot!

Boston Scientific Subcutaneous Implantable Cardiodefibrillator Device S-ICD

Now because the ‘Vectors’ used by the S-ICD are over a larger area than those with a traditional device – more energy has to be delivered to have the same desired affect. The upshot of this is that a larger battery is required to deliver the 80J! Bigger Battery = Bigger Box. This image shows a demo device but this is the exact size compared to a One Pound Coin! Now yes it is big but because of the extra room where they place the device it is pretty discrete and hidden in even slender patients.
STAT ATTACK!
The S-ICD System delivers up to 5 shocks per episode at 80 J with up to 128 seconds of ECG storage per episode and storage of up to 45 episodes.
The heart rate that the S-ICD is told to deliver therapy is programable between 170 and 250 bpm. Quite cleverly the device is able to also deliver a small amount of ‘pacing’ after a shock, when the heart can often run slowly. This is external pacing and will be felt!! It can run for 30s.

Sensing in an S-ICD.

 
The S-ICD uses its electrodes to produce an ECG similar to a surface ECG. 
 
Now the Sensing functionality is the devices ability to determine what Rhythm the heart is in! Without a lead in the heart to give us really accurate information the device is using a large area of heart, ribs and muscle. This means there is more potential for ‘artefact’. Artefact is the electrical interference and confusion – that could potentially lead to a patient being shocked when they do not require it – or not being shocked when they do…
Boston Scientific have come up with a very clever software/algorithm called ‘Insight’. Insight uses 3 separate methods to determine the nature of a heart rhythm.
  • Normal Sinus Rhythm Template (Do your heart beats look as they should)
  • Dynamic Morphology Analysis (A live comparison of heart beat to previous heart beat, do they all look the same or do they keep changing?)
  • QRS Width analysis (Are the tall ‘peaks’ on your ECG, the QRS’, wider than they normally are?)
These questions (with some very complex maths) and the rate of a rhythm are used to decide whether to ‘shock’ or not.
Insight Algorithm S-ICD

Image Courtesy of  http://www.bostonscientific.com/

How does Insight and the S-ICD compare to other ICD Devices?

The statistics for treatment success and inappropriate shocks (an electrocuted patient that did not need to be) actually compare very similarly if not favourably compared to other devices on the market – these two studies are well worth a read if you have the time 🙂
1. Burke M, et al. Safety and Efficacy of a Subcutaneous Implantable-Debrillator (S-ICD System US IDE Study). Late-Breaking Abstract Session. HRS 2012.
2. Lambiase PD, et al. International Experience with a Subcutaneous ICD; Preliminary Results of the EFFORTLESS S-ICD Registry. Cardiostim 2012.
3. Gold MR, et al. Head-to-head comparison of arrhythmia discrimination performance of subcutaneous and transvenous ICD arrhythmia detection algorithms: the START study. J Cardiovasc Electrophysiol. 2012;23;4:359-366.
Who qualifies?
Template S-ICD Eligibility

Template used to assess eligibility!
Image Courtesy of
http://www.bostonscientific.com/
Well essentially anyone who qualifies for a normal ‘shock box’ ICD but with one other requirement. The Insight Software requires that a person has certain characteristics on their ECG. This is essentially showing that they have tall enough and narrow enough complexes to allow the algorithm to perform effectively. A simple 12 lead ECG Laying and Standing will be obtained and then a ‘Stencil’ is passed over the Print out – If the complexes fit within the boundaries marked on the ‘stencil’ then you potentially qualify. If your ECG does not meet requirements then it will not be recommended for you to have the S-ICD.

There you have it a quick overview of the Boston Scientific S-ICD.

Thanks for Reading

Cardiac Technician

SOURCE

http://www.thepad.pm/2013/12/boston-scientific-s-icd.html#!

UPDATED on 10/15/2013

Frequency and Determinants of Implantable Cardioverter Defibrillator Deployment Among Primary Prevention Candidates With Subsequent Sudden Cardiac Arrest in the Community

  1. Kumar Narayanan, MD;
  2. Kyndaron Reinier, PhD;
  3. Audrey Uy-Evanado, MD;
  4. Carmen Teodorescu, MD, PhD;
  5. Harpriya Chugh, BS;
  6. Eloi Marijon, MD;
  7. Karen Gunson, MD;
  8. Jonathan Jui, MD, MPH;
  9. Sumeet S. Chugh, MD

+Author Affiliations


  1. From The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA (K.N., K.R., A.U.-E., C.T., H.C., E.M., S.S.C.); and Departments of Pathology (K.G.) and Emergency Medicine (J.J.), Oregon Health and Science University, Portland, OR.
  1. Correspondence to Sumeet S. Chugh, MD, Cedars-Sinai Medical Center, The Heart Institute, AHSP Suite A3100, 127 S. San Vicente Blvd., Los Angeles, CA 90048, Los Angeles, CA 90048. E-mail sumeet.chugh@cshs.org

Abstract

Background—The prevalence rates and influencing factors for deployment of primary prevention implantable cardioverter defibrillators (ICDs) among subjects who eventually experience sudden cardiac arrest in the general population have not been evaluated.

Methods and Results—Cases of adult sudden cardiac arrest with echocardiographic evaluation before the event were identified from the ongoing Oregon Sudden Unexpected Death Study (population approximately 1 million). Eligibility for primary ICD implantation was determined from medical records based on established guidelines. The frequency of prior primary ICD implantation in eligible subjects was evaluated, and ICD nonrecipients were characterized. Of 2093 cases (2003–2012), 448 had appropriate pre– sudden cardiac arrest left ventricular ejection fraction information available. Of these, 92 (20.5%) were eligible for primary ICD implantation, 304 (67.9%) were ineligible because of left ventricular ejection fraction >35%, and the remainder (52, 11.6%) had left ventricular ejection fraction ≤35% but were ineligible on the basis of clinical guideline criteria. Among eligible subjects, only 12 (13.0%; 95% confidence interval, 6.1%–19.9%) received a primary ICD. Compared with recipients, primary ICD nonrecipients were older (age at ejection fraction assessment, 67.1±13.6 versus 58.5±14.8 years, P=0.05), with 20% aged ≥80 years (versus 0% among recipients, P=0.11). Additionally, a subgroup (26%) had either a clinical history of dementia or were undergoing chronic dialysis.

Conclusions—Only one fifth of the sudden cardiac arrest cases in the community were eligible for a primary prevention ICD before the event, but among these, a small proportion (13%) were actually implanted. Although older age and comorbidity may explain nondeployment in a subgroup of these cases, other determinants such as socioeconomic factors, health insurance, patient preference, and clinical practice patterns warrant further detailed investigation.

Key Words:

  • Received March 11, 2013.
  • Accepted August 21, 2013

http://circ.ahajournals.org/content/128/16/1733.abstract

UPDATED on 9/15/2013

based on 9/6/2013 Trials and Fibrillations — The Heart.org

http://www.theheart.org/columns/trials-and-fibrillations-with-dr-john-mandrola/new-post-39.do#!

Echo-CRT trial: Most important study released at ESC 2013

Cardiac resynchronization therapy (CRT) is a multilead pacing device that can extend lives and improve the quality of life of selected patients who suffer from reduced performance of the heart due to adverse timing of contraction (wobbling motion from conduction delays that cause asynchrony or  delayed activation of one portion of the left ventricle compared to others reducing net blood ejection).

The degree of benefit in CRT responders depends not only on the degree of asynchrony, but also on the delayed activity location in relation to the available locations for lead placement. CRT is an adjustment in the timing of muscle activiation to improve the concerted impact on blood ejection. Only patients likely to improve should be exposed to the risks and costs of CRT.

The Echo-CRT trial, presented September 3, 2013 at the European Society of Cardiology (ESC) 2013 Congressand simultaneously published in the New England Journal of Medicine, helps identify which patients may benefit from CRT devices. (See Steve Stiles’ report on heartwire),

Echo-CRT trial summary

Background is important

Previous CRT studies enrolled patients with QRS duration >120 or >130 ms for synchronizing biventricular pacing. Additional work confirmed the greatest benefit occurred in patients with QRS durations >150 ms and typical left bundle branch block (LBBB). Conflicting observational and small randomized trials were less clear for patients with shorter QRS durations—the majority of heart-failure patients. What’s more, most cardiologists have seen patients with “modest” QRS durations respond to CRT. In theory, wide QRS is only expected if the axis of significant delay projects onto the standard ECG views, whereas significant opportunity for benefit can be missed if the axis of significant delay is not wide in the standard views. CRT implanters have heard of patients with normal-duration QRS where echo shows marked dyssynchrony. This raised the  question: Are there CHF patients with mechanical dyssynchrony (determined by echo) but no electrical delay (as measured by the ECG) benefit from CRT?Unfortunately, echo does not resolve the issue either. Thus there is the residual question of who should be evaluated by a true 3D syncrhony assessment by cardiac MRI.

Echocardiographic techniques held promise to identify mechanical dyssynchrony, but like the standard 12 lead ECG, they also utilize limited orientations of views of the heart and hence the directions in which delays can be detected. Cardiac MRI Research (not limited in view angle) by JDPearlman showed that the axis of maximal delay in patients with asynchrony is within 30 degrees of the ECG and echo views in a majority of patients with asynchrony, but it can be 70-110 degrees away from the views used by echocardiography and by ECG in 20% of cases. Hence some patients who may benefit can be missed by ECG or Echo criteria.

Methodology

Echo-CRT was an industry-sponsored (Biotronik) investigator-initiated prospective international randomized controlled trial. All patients had mechanical dyssynchrony by echo, QRS <130 ms, and an ICD indication. CRT-D devices were implanted in all patients. Blinded randomization to CRT-on (404 patients) vs CRT-off (405 patients) was performed after implantation. Programming in the CRT-off group was set to minimize RV pacing. The primary outcome was a composite of all-cause mortality or hospitalization.

Six key findings

1. Although entry criteria for the trial was a QRS duration <130 ms, the mean QRS duration of both groups was 105 ms.

2. The data safety monitoring board terminated the trial prematurely because of an increased death rate in the CRT group.

3. No differences were noted in the primary outcome.

4. More patients died in the CRT group (hazard ratio=1.8).

5. The higher death rate in the CRT group was driven by cardiovascular death.

6. More patients in the CRT group were hospitalized, due primarily to device-related issues.

These findings send clear and simple messages to all involved with treating patients with heart failure. My interpretation of Echo-CRT is as follows:

Do not implant CRT devices in patients with “narrow” QRS complexes.

The signal of increased death was strong. A hazard ratio of 1.8 translates to an almost doubling of the risk of death. This finding is unlikely to be a statistical anomaly, as it was driven by CV death. The risks of CRT in nonresponders are well-known and include: increased RV pacing, possible proarrhythmia from LV pacing, and the need for more device-related surgery. Patients who do not respond to CRT get none of the benefits but all the potential harms—an unfavorable ratio indeed.

Echo is not useful for assessing dyssynchrony in patients with narrow QRS complexes.

Dr Samuel Asirvatham explains the concept of electropathy in a review article in the Journal of Cardiovascular Electrophysiology. He teaches us that the later the LV lateral wall is activated relative to the RV, the more the benefit of preexciting the lateral wall with an LV lead. That’s why the benefit from CRT in many cases increases with QRS duration, because—in a majority—a wide QRS means late activation of the lateral LV.

Simple triumphs over complicated—CRT response best estimated with the old-fashioned ECG.

In a right bundle branch block, the left ventricle is activated first; in LBBB, the LV lateral wall is last, and with a nonspecific ICD, there’s delayed conduction in either the His-Purkinje system or in ventricular muscle. What does a normal QRS say? It says the wave front of activation as projected onto the electric views obtained activates the LV and RV simultaneously. If those views capture the worst delay then they can eliminate the  need for resynchrony.

CRT benefit with mild-moderate QRS prolongation still not settled

Dr Robert Myerburg (here and here) teaches us to make a distinction between trial entry criteria and the actual values of the cohort.

Consider how this applies to QRS duration:  COMPANION and CARE-HF are clinical trials that showed definitive CRT benefit. Entry required a QRS duration >120 ms (130 ms in CARE-HF). But the actual mean QRS duration of enrolled patients was 160 ms. A meta-analysis of CRT trials confirmed benefit at longer QRS durations and questioned it below 150 ms. CRT guideline recommendations incorporate study entry criteria, not the mean values of actual patients in the trial. Patients enrolled in Echo-CRT had very narrow QRS complexes (105 ms). What to recommend in the common situation when a patient with a typical LBBB has a QRS duration straddling 130 ms is not entirely clear. The results of Echo-CRT might have been different had the actual QRS duration values been closer to 130 ms.

Conclusion

Echo-CRT study reinforces expectations based on cardiac physiology. In the practice of medicine, it’s quite useful to know when not to do something.

The trial should not dampen enthusiasm for CRT. Rather, it should focus our attention to patient selection—and the value of the 12-lead ECG.

 References

Rethinking QRS Duration as an Indication for CRT

SMITA MEHTA M.D.1 and SAMUEL J. ASIRVATHAM M.D., F.A.C.C.2,3

Author Information

  1. Department of Pediatric Cardiology, Cleveland Clinic, Cleveland, Ohio, USA
  2. Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
  3. Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota, USA

*Samuel J. Asirvatham, M.D., Division of Cardiovascular Diseases, Department of Internal Medicine and Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. E-mail: asirvatham.samuel@mayo.edu

J Cardiovasc Electrophysiol, Vol. 23, pp. 169-171, February 2012.

http://onlinelibrary.wiley.com/doi/10.1111/j.1540-8167.2011.02163.x/full

Indications for Implantable Cardioverter-Defibrillators Based on Evidence and Judgment FREE

Robert J. Myerburg, MD; Vivek Reddy, MD; Agustin Castellanos, MD
J Am Coll Cardiol. 2009;54(9):747-763. doi:10.1016/j.jacc.2009.03.078

Implantable Cardioverter–Defibrillators after Myocardial Infarction

Robert J. Myerburg, M.D.

Division of Cardiology, University of Miami Miller School of Medicine, Miami.

N Engl J Med 2008; 359:2245-2253 November 20, 2008DOI: 10.1056/NEJMra0803409

END OF UPDATE

Electrical conduction of the Human Heart

  • Physiology and
  • Genetics

were explained by us in the following articles:

Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

On Devices and On Algorithms: Prediction of Arrhythmia after Cardiac Surgery and ECG Prediction of an Onset of Paroxysmal Atrial Fibrillation

Dilated Cardiomyopathy: Decisions on implantable cardioverter-defibrillators (ICDs) using left ventricular ejection fraction (LVEF)

Reduction in Inappropriate Therapy and Mortality through ICD Programming

Below, we present the following complementary topics:

Options for Cardiac Resynchronization Therapy (CRT) to Arrhythmias:

  • Implantable Pacemaker
  • Insertable Programmable Cardioverter Defibrillator (ICD)

UPDATED 8/6/2013

Medtronic Pacemaker Recall

 

17/07/2013

Australia’s regulatory authority, the Therapeutic Goods Administration (TGA) has issued a hazard alert pertaining to one of Medtronic’s pacing devices, the Consulta® Cardiac Resynchronization Therapy Pacemaker (CRT-P). The alert coincides somewhat with Medtronic’s own issuance of a field safety notice concerning Consulta and Syncra® CRT-P devices.

Background

Consulta and Syncra CRT-Ps are implantable medical devices used to treat heart failure. The devices provide pacing to help coordinate the heart’s pumping action and improve blood flow.

The two devices are the subject of a global manufacturer recall after Medtronic had identified an issue with a subset of both during production, although as yet there had been no reported or confirmed device failures. However, because of the potential for malfunction, Medtronic is requiring the return of non-implanted devices manufactured between April 1 and May 13, 2013 for re-inspection.

Seemingly this manufacturing issue could compromise the sealing of the device. Should an out-of-spec weld fail this could result in body fluids entering the device, which could cause it to malfunction leading to loss of pacing output. This could potentially see the return of symptoms including

  • fainting or lightheadedness,
  • dyspnoea (shortness of breath),
  • fatigue and
  • oedema.

Medtronic’s recall is thought to relate to 265 devices, 44 of which have been implanted in the US.

The Australian warning letter, issued by the TGA states that only one “at risk” Consulta CRT-P device has been implanted in the country and there have been no reports of device failures or patient injuries relating to this issue.

Neither Medtronic nor the TGA are suggesting any specific patient management measures other than routine follow-up in accordance with labelling instructions.

Pacemaker/Implantable Cardioverter Defibrillator (ICD) Insertion

Procedure Overview

What is a pacemaker/implantable cardioverter defibrillator (ICD) insertion?

A pacemaker/implantable cardioverter defibrillator (ICD) insertion is a procedure in which a pacemaker and/or an ICD is inserted to assist in regulating problems with the heart rate (pacemaker) or heart rhythm (ICD).

Pacemaker

When a problem develops with the heart’s rhythm, such as a slow rhythm, a pacemaker may be selected for treatment. A pacemaker is a small electronic device composed of three parts: a generator, one or more leads, and an electrode on each lead. A pacemaker signals the heart to beat when the heartbeat is too slow.

Illustration of a single-chamber pacemaker
Click Image to Enlarge

A generator is the “brain” of the pacemaker device. It is a small metal case that contains electronic circuitry and a battery. The lead (or leads) is an insulated wire that is connected to the generator on one end, with the other end placed inside one of the heart’s chambers.

The electrode on the end of the lead touches the heart wall. In most pacemakers, the lead senses the heart’s electrical activity. This information is relayed to the generator by the lead.

If the heart’s rate is slower than the programmed limit, an electrical impulse is sent through the lead to the electrode and the pacemaker’s electrical impulse causes the heart to beat at a faster rate.

When the heart is beating at a rate faster than the programmed limit, the pacemaker will monitor the heart rate, but will not pace. No electrical impulses will be sent to the heart unless the heart’s natural rate falls below the pacemaker’s low limit.

Pacemaker leads may be positioned in the atrium or ventricle or both, depending on the condition requiring the pacemaker to be inserted. An atrial dysrhythmia/arrhythmia (an abnormal heart rhythm caused by a dysfunction of the sinus node or the development of another atrial pacemaker within the heart tissue that takes over the function of the sinus node) may be treated with an atrial pacemaker.

Illustration of a dual-chamber pacemaker
Click Image to Enlarge

A ventricular dysrhythmia/arrhythmia (an abnormal heart rhythm caused by a dysfunction of the sinus node, an interruption in the conduction pathways, or the development of another pacemaker within the heart tissue that takes over the function of the sinus node) may be treated with a ventricular pacemaker whose lead wire is located in the ventricle.

It is possible to have both atrial and ventricular dysrhythmias, and there are pacemakers that have lead wires positioned in both the atrium and the ventricle. There may be one lead wire for each chamber, or one lead wire may be capable of sensing and pacing both chambers.

A new type of pacemaker, called a biventricular pacemaker, is currently used in the treatment of congestive heart failure. Sometimes in heart failure, the two ventricles (lower heart chambers) do not pump together in a normal manner. When this happens, less blood is pumped by the heart.

A biventricular pacemaker paces both ventricles at the same time, increasing the amount of blood pumped by the heart. This type of treatment is called cardiac resynchronization therapy.

Implantable cardioverter defibrillator (ICD)

An implantable cardioverter defibrillator (ICD) looks very similar to a pacemaker, except that it is slightly larger. It has a generator, one or more leads, and an electrode for each lead. These components work very much like a pacemaker. However, the ICD is designed to deliver an electrical shock to the heart when the heart rate becomes dangerously fast, or €œfibrillates.”

An ICD senses when the heart is beating too fast and delivers an electrical shock to convert the fast rhythm to a normal rhythm. Some devices combine a pacemaker and ICD in one unit for persons who need both functions.

The ICD has another type of treatment for certain fast rhythms called anti-tachycardia pacing (ATP). When ATP is used, a fast pacing impulse is sent to correct the rhythm. After the shock is delivered, a “back-up” pacing mode is used if needed for a short while.

The procedure for inserting a pacemaker or an ICD is the same. The procedure generally is performed in an electrophysiology (EP) lab or a cardiac catheterization lab.

Other related procedures that may be used to assess the heart include resting and exercise electrocardiogram (ECG), Holter monitor, signal-averaged ECG, cardiac catheterization, chest x-ray, computed tomography (CT scan) of the chest, echocardiography, electrophysiology studies, magnetic resonance imaging (MRI) of the heart, myocardial perfusion scans, radionuclide angiography, and ultrafast CT scan.

The heart’s electrical conduction system

Illustration of the anatomy of the heart, view of the electrical system
Click Image to Enlarge

The heart is, in the simplest terms, a pump made up of muscle tissue. Like all pumps, the heart requires a source of energy in order to function. The heart’s pumping energy comes from an indwelling electrical conduction system.

An electrical stimulus is generated by the sinus node (also called the sinoatrial node, or SA node), which is a small mass of specialized tissue located in the right atrium (right upper chamber) of the heart.

The sinus node generates an electrical stimulus regularly at 60 to 100 times per minute under normal conditions. This electrical stimulus travels down through the conduction pathways (similar to the way electricity flows through power lines from the power plant to your house) and causes the heart’s chambers to contract and pump out blood.

The right and left atria (the two upper chambers of the heart) are stimulated first and contract a short period of time before the right and left ventricles (the two lower chambers of the heart).

The electrical impulse travels from the sinus node to the atrioventricular (AV) node, where it stops for a very short period, then continues down the conduction pathways via the “bundle of His” into the ventricles. The bundle of His divides into right and left pathways to provide electrical stimulation to both ventricles.

What is an ECG?

This electrical activity of the heart is measured by an electrocardiogram (ECG or EKG). By placing electrodes at specific locations on the body (chest, arms, and legs), a tracing of the electrical activity can be obtained. Changes in an ECG from the normal tracing can indicate one or more of several heart-related conditions.

Dysrhythmias/arrhythmias (abnormal heart rhythms) are diagnosed by methods such as EKG, Holter monitoring, signal-average EKG, or electrophysiological studies. These symptoms may be treated with medication or procedures such as a cardiac ablation (removal of a location in the heart that is causing a dysrhythmia by freezing or radiofrequency).

Reasons for the Procedure

A pacemaker may be inserted in order to provide stimulation for a faster heart rate when the heart is beating too slowly, and when other treatment methods, such as medication, have not improved the heart rate.

An ICD may be inserted in order to provide fast pacing (ATP), cardioversion (small shock), or defibrillation (larger shock) when the heart beats too fast.

Problems with the heart rhythm may cause difficulties because the heart is unable to pump an adequate amount of blood to the body. If the heart rate is too slow, the blood is pumped too slowly.

If the heart rate is too fast or too irregular, the heart chambers are unable to fill up with enough blood to pump out with each beat. When the body does not receive enough blood, symptoms such as fatigue, dizziness, fainting, and/or chest pain may occur.

Some examples of rhythm problems for which a pacemaker or ICD might be inserted include:

  • atrial fibrillation – occurs when the atria beat irregularly and too fast
  • ventricular fibrillation – occurs when the ventricles beat irregularly and too fast
  • bradycardia – occurs when the heart beats too slow
  • tachycardia – occurs when the heart beats too fast
  • heart block – occurs when the electrical signal is delayed after leaving the SA node; there are several types of heart blocks, and each one has a distinctive ECG tracing

There may be other reasons for your physician to recommend a pacemaker or ICD insertion.

Risks of the Procedure

Possible risks of pacemaker or ICD insertion include, but are not limited to, the following:

  • bleeding from the incision or catheter insertion site
  • damage to the vessel at the catheter insertion site
  • infection of the incision or catheter site
  • pneumothorax – air becomes trapped in the pleural space causing the lung to collapse

If you are pregnant or suspect that you may be pregnant, you should notify your physician. If you are lactating, or breastfeeding, you should notify your physician.

Patients who are allergic to or sensitive to medications or latex should notify their physician.

For some patients, having to lie still on the procedure table for the length of the procedure may cause some discomfort or pain.

There may be other risks depending upon your specific medical condition. Be sure to discuss any concerns with your physician prior to the procedure.

Before the Procedure

  • Your physician will explain the procedure to you and offer you the opportunity to ask any questions that you might have about the procedure.
  • You will be asked to sign a consent form that gives your permission to do the test. Read the form carefully and ask questions if something is not clear.
  • You will need to fast for a certain period of time prior to the procedure. Your physician will notify you how long to fast, usually overnight.
  • If you are pregnant or suspect that you are pregnant, you should notify your physician.
  • Notify your physician if you are sensitive to or are allergic to any medications, iodine, latex, tape, or anesthetic agents (local and general).
  • Notify your physician of all medications (prescription and over-the-counter) and herbal supplements that you are taking.
  • Notify your physician if you have heart valve disease, as you may need to receive an antibiotic prior to the procedure.
  • Notify your physician if you have a history of bleeding disorders or if you are taking any anticoagulant (blood-thinning) medications, aspirin, or other medications that affect blood clotting. It may be necessary for you to stop some of these medications prior to the procedure.
  • Your physician may request a blood test prior to the procedure to determine how long it takes your blood to clot. Other blood tests may be done as well.
  • You may receive a sedative prior to the procedure to help you relax. If a sedative is given, you will need someone to drive you home afterwards.
  • The upper chest may be shaved or clipped prior to the procedure.
  • Based upon your medical condition, your physician may request other specific preparation.

During the Procedure

Picture of a chest X-ray, showing a single-chamber implanted pacemaker
Chest X-ray with Implanted Pacemaker

A pacemaker or implanted cardioverter defibrillator may be performed on an outpatient basis or as part of your stay in a hospital. Procedures may vary depending on your condition and your physician’s practices.

Generally, a pacemaker or ICD insertion follows this process:

  1. You will be asked to remove any jewelry or other objects that may interfere with the procedure.
  2. You will be asked to remove your clothing and will be given a gown to wear.
  3. You will be asked to empty your bladder prior to the procedure.
  4. An intravenous (IV) line will be started in your hand or arm prior to the procedure for injection of medication and to administer IV fluids, if needed.
  5. You will be placed in a supine (on your back) position on the procedure table.
  6. You will be connected to an electrocardiogram (ECG or EKG) monitor that records the electrical activity of the heart and monitors the heart during the procedure using small, adhesive electrodes. Your vital signs (heart rate, blood pressure, breathing rate, and oxygenation level) will be monitored during the procedure.
  7. Large electrode pads will be placed on the front and back of the chest.
  8. You will receive a sedative medication in your IV before the procedure to help you relax. However, you will likely remain awake during the procedure.
  9. The pacemaker or ICD insertion site will be cleansed with antiseptic soap.
  10. Sterile towels and a sheet will be placed around this area.
  11. A local anesthetic will be injected into the skin at the insertion site.
  12. Once the anesthetic has taken effect, the physician will make a small incision at the insertion site.
  13. A sheath, or introducer, is inserted into a blood vessel, usually under the collarbone. The sheath is a plastic tube through which the pacer/ICD lead wire will be inserted into the blood vessel and advanced into the heart.
  14. It will be very important for you to remain still during the procedure so that the catheter placement will not be disturbed and to prevent damage to the insertion site.
  15. The lead wire will be inserted through the introducer into the blood vessel. The physician will advance the lead wire through the blood vessel into the heart.
  16. Once the lead wire is inside the heart, it will be tested to verify proper location and that it works. There may be one, two, or three lead wires inserted, depending on the type of device your physician has chosen for your condition. Fluoroscopy, (a special type of x-ray that will be displayed on a TV monitor), may be used to assist in testing the location of the leads.
  17. Once the lead wire has been tested, an incision will be made close to the location of the catheter insertion (just under the collarbone). You will receive local anesthetic medication before the incision is made.
  18. The pacemaker/ICD generator will be slipped under the skin through the incision after the lead wire is attached to the generator. Generally, the generator will be placed on the non-dominant side. (If you are right-handed, the device will be placed in your upper left chest. If you are left-handed, the device will be placed in your upper right chest).
  19. The ECG will be observed to ensure that the pacer is working correctly.
  20. The skin incision will be closed with sutures, adhesive strips, or a special glue.
  21. A sterile bandage/dressing will be applied.

After the Procedure

In the hospital

After the procedure, you may be taken to the recovery room for observation or returned to your hospital room. A nurse will monitor your vital signs for a specified period of time.

You should immediately inform your nurse if you feel any chest pain or tightness, or any other pain at the incision site.

After the specified period of bed rest has been completed, you may get out of bed. The nurse will assist you the first time you get up, and will check your blood pressure while you are lying in bed, sitting, and standing. You should move slowly when getting up from the bed to avoid any dizziness from the period of bedrest.

You will be able to eat or drink once you are completely awake.

The insertion site may be sore or painful, but pain medication may be administered if needed.

Your physician will visit with you in your room while you are recovering. The physician will give you specific instructions and answer any questions you may have.

Once your blood pressure, pulse, and breathing are stable and you are alert, you will be taken to your hospital room or discharged home.

If the procedure is performed on an outpatient basis, you may be allowed to leave after you have completed the recovery process. However, if there are concerns or problems with your ECG, you may stay in the hospital for an additional day (or longer) for monitoring of the ECG.

You should arrange to have someone drive you home from the hospital following your procedure.

At home

You should be able to return to your daily routine within a few days. Your physician will tell you if you will need to take more time in returning to your normal activities. In addition, you should not do any lifting or pulling on anything for a few weeks. You may be instructed not to lift your arms above your head for a period of time.

You will most likely be able to resume your usual diet, unless your physician instructs you differently.

It will be important to keep the insertion site clean and dry. Your physician will give you specific bathing instructions.

Your physician will give you specific instructions about driving. If you had an ICD, you will not be able to drive until your physician gives you approval. Your physician will explain these limitations to you, if they are applicable to your situation.

You will be given specific instructions about what to do if your ICD discharges a shock. For example, you may be instructed to dial 911 or go to the nearest emergency room in the event of a shock from the ICD.

Ask your physician when you will be able to return to work. The nature of your occupation, your overall health status, and your progress will determine how soon you may return to work.

Notify your physician to report any of the following:

  • fever and/or chills
  • increased pain, redness, swelling, or bleeding or other drainage from the insertion site
  • chest pain/pressure, nausea and/or vomiting, profuse sweating, dizziness and/or fainting
  • palpitations

Your physician may give you additional or alternate instructions after the procedure, depending on your particular situation.

Pacemaker/ICD precautions

The following precautions should always be considered. Discuss the following in detail with your physician, or call the company that made your device:

  • Always carry an ID card that states you are wearing a pacemaker or an ICD. In addition, you should wear a medical identification bracelet that states you have a pacemaker or ICD.
  • Use caution when going through airport security detectors. Check with your physician about the safety of going through such detectors with your type of pacemaker. In particular, you may need to avoid being screened by hand-held detector devices, as these devices may affect your pacemaker.
  • You may not have a magnetic resonance imaging (MRI) procedure. You should also avoid large magnetic fields.
  • Abstain from diathermy (the use of heat in physical therapy to treat muscles).
  • Turn off large motors, such as cars or boats, when working on them (they may temporarily €œconfuse” your device).
  • Avoid certain high-voltage or radar machinery, such as radio or television transmitters, electric arc welders, high-tension wires, radar installations, or smelting furnaces.
  • If you are having a surgical procedure performed by a surgeon or dentist, tell your surgeon or dentist that you have a pacemaker or ICD, so that electrocautery will not be used to control bleeding (the electrocautery device can change the pacemaker settings).
  • You may have to take antibiotic medication before any medically invasive procedure to prevent infections that may affect the pacemaker.
  • Always consult your physician if you have any questions concerning the use of certain equipment near your pacemaker.
  • When involved in a physical, recreational, or sporting activity, you should avoid receiving a blow to the skin over the pacemaker or ICD. A blow to the chest near the pacemaker or ICD can affect its functioning. If you do receive a blow to that area, see your physician.
  • Always consult your physician when you feel ill after an activity, or when you have questions about beginning a new activity.

SOURCE

http://stanfordhospital.org/healthLib/greystone/heartCenter/heartProcedures/pacemakerImplantableCardioverterDefibrillatorICDInsertion.html

In Summary: Who Needs a Pacemaker?

Doctors recommend pacemakers for many reasons. The most common reasons are bradycardia and heart block.

Bradycardia is a heartbeat that is slower than normal. Heart block is a disorder that occurs if an electrical signal is slowed or disrupted as it moves through the heart.

Heart block can happen as a result of aging, damage to the heart from a heart attack, or other conditions that disrupt the heart’s electrical activity. Some nerve and muscle disorders also can cause heart block, including muscular dystrophy.

Your doctor also may recommend a pacemaker if:

  • Aging or heart disease damages your sinus node’s ability to set the correct pace for your heartbeat. Such damage can cause slower than normal heartbeats or long pauses between heartbeats. The damage also can cause your heart to switch between slow and fast rhythms. This condition is called sick sinus syndrome.
  • You’ve had a medical procedure to treat an arrhythmia called atrial fibrillation. A pacemaker can help regulate your heartbeat after the procedure.
  • You need to take certain heart medicines, such as beta blockers. These medicines can slow your heartbeat too much.
  • You faint or have other symptoms of a slow heartbeat. For example, this may happen if the main artery in your neck that supplies your brain with blood is sensitive to pressure. Just quickly turning your neck can cause your heart to beat slower than normal. As a result, your brain might not get enough blood flow, causing you to feel faint or collapse.
  • You have heart muscle problems that cause electrical signals to travel too slowly through your heart muscle. Your pacemaker may provide cardiac resynchronization therapy (CRT) for this problem. CRT devices coordinate electrical signaling between the heart’s lower chambers.
  • You have long QT syndrome, which puts you at risk for dangerous arrhythmias.

Doctors also may recommend pacemakers for people who have certain types ofcongenital heart disease or for people who have had heart transplants. Children, teens, and adults can use pacemakers.

Before recommending a pacemaker, your doctor will consider any arrhythmia symptoms you have, such as dizziness, unexplained fainting, or shortness of breath. He or she also will consider whether you have a history of heart disease, what medicines you’re currently taking, and the results of heart tests.

Diagnostic Tests

Many tests are used to detect arrhythmias. You may have one or more of the following tests.

EKG (Electrocardiogram)

An EKG is a simple, painless test that detects and records the heart’s electrical activity. The test shows how fast your heart is beating and its rhythm (steady or irregular).

An EKG also records the strength and timing of electrical signals as they pass through your heart. The test can help diagnose bradycardia and heart block (the most common reasons for needing a pacemaker).

A standard EKG only records the heartbeat for a few seconds. It won’t detect arrhythmias that don’t happen during the test.

To diagnose heart rhythm problems that come and go, your doctor may have you wear a portable EKG monitor. The two most common types of portable EKGs are Holter and event monitors.

Holter and Event Monitors

A Holter monitor records the heart’s electrical activity for a full 24- or 48-hour period. You wear one while you do your normal daily activities. This allows the monitor to record your heart for a longer time than a standard EKG.

An event monitor is similar to a Holter monitor. You wear an event monitor while doing your normal activities. However, an event monitor only records your heart’s electrical activity at certain times while you’re wearing it.

For many event monitors, you push a button to start the monitor when you feel symptoms. Other event monitors start automatically when they sense abnormal heart rhythms.

You can wear an event monitor for weeks or until symptoms occur.

Echocardiography

Echocardiography (echo) uses sound waves to create a moving picture of your heart. The test shows the size and shape of your heart and how well your heart chambers and valves are working.

Echo also can show areas of poor blood flow to the heart, areas of heart muscle that aren’t contracting normally, and injury to the heart muscle caused by poor blood flow.

Electrophysiology Study

For this test, a thin, flexible wire is passed through a vein in your groin (upper thigh) or arm to your heart. The wire records the heart’s electrical signals.

Your doctor uses the wire to electrically stimulate your heart. This allows him or her to see how your heart’s electrical system responds. This test helps pinpoint where the heart’s electrical system is damaged.

Stress Test

Some heart problems are easier to diagnose when your heart is working hard and beating fast.

During stress testing, you exercise to make your heart work hard and beat fast while heart tests, such as an EKG or echo, are done. If you can’t exercise, you may be given medicine to raise your heart rate.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/whoneeds.html

What Are the Risks of Pacemaker Surgery?

Pacemaker surgery generally is safe. If problems do occur, they may include:

  • Swelling, bleeding, bruising, or infection in the area where the pacemaker was placed
  • Blood vessel or nerve damage
  • A collapsed lung
  • A bad reaction to the medicine used during the procedure

Talk with your doctor about the benefits and risks of pacemaker surgery.

How Does a Pacemaker Work?

A pacemaker consists of a battery, a computerized generator, and wires with sensors at their tips. (The sensors are called electrodes.) The battery powers the generator, and both are surrounded by a thin metal box. The wires connect the generator to the heart.

A pacemaker helps monitor and control your heartbeat. The electrodes detect your heart’s electrical activity and send data through the wires to the computer in the generator.

If your heart rhythm is abnormal, the computer will direct the generator to send electrical pulses to your heart. The pulses travel through the wires to reach your heart.

Newer pacemakers can monitor your blood temperature, breathing, and other factors. They also can adjust your heart rate to changes in your activity.

The pacemaker’s computer also records your heart’s electrical activity and heart rhythm. Your doctor will use these recordings to adjust your pacemaker so it works better for you.

Your doctor can program the pacemaker’s computer with an external device. He or she doesn’t have to use needles or have direct contact with the pacemaker.

Pacemakers have one to three wires that are each placed in different chambers of the heart.

  • The wires in a single-chamber pacemaker usually carry pulses from the generator to the right ventricle (the lower right chamber of your heart).
  • The wires in a dual-chamber pacemaker carry pulses from the generator to the right atrium (the upper right chamber of your heart) and the right ventricle. The pulses help coordinate the timing of these two chambers’ contractions.
  • The wires in a biventricular pacemaker carry pulses from the generator to an atrium and both ventricles. The pulses help coordinate electrical signaling between the two ventricles. This type of pacemaker also is called a cardiac resynchronization therapy (CRT) device.

Cross-Section of a Chest With a Pacemaker

The image shows a cross-section of a chest with a pacemaker. Figure A shows the location and general size of a double-lead, or dual-chamber, pacemaker in the upper chest. The wires with electrodes are inserted into the heart's right atrium and ventricle through a vein in the upper chest. Figure B shows an electrode electrically stimulating the heart muscle. Figure C shows the location and general size of a single-lead, or single-chamber, pacemaker in the upper chest.

The image shows a cross-section of a chest with a pacemaker. Figure A shows the location and general size of a double-lead, or dual-chamber, pacemaker in the upper chest. The wires with electrodes are inserted into the heart’s right atrium and ventricle through a vein in the upper chest. Figure B shows an electrode electrically stimulating the heart muscle. Figure C shows the location and general size of a single-lead, or single-chamber, pacemaker in the upper chest.

Types of Pacemaker Programming

The two main types of programming for pacemakers are

  • demand pacing and
  • rate-responsive pacing.

A demand pacemaker monitors your heart rhythm. It only sends electrical pulses to your heart if your heart is beating too slow or if it misses a beat.

A rate-responsive pacemaker will speed up or slow down your heart rate depending on how active you are. To do this, the device monitors your

  • sinus node rate,
  • breathing,
  • blood temperature, and
  • other factors to determine your activity level.

Your doctor will work with you to decide which type of pacemaker is best for you.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/howdoes.html

What To Expect During Pacemaker Surgery

Placing a pacemaker requires minor surgery. The surgery usually is done in a hospital or special heart treatment laboratory.

Before the surgery, an intravenous (IV) line will be inserted into one of your veins. You will receive medicine through the IV line to help you relax. The medicine also might make you sleepy.

Your doctor will numb the area where he or she will put the pacemaker so you don’t feel any pain. Your doctor also may give you antibiotics to prevent infection.

First, your doctor will insert a needle into a large vein, usually near the shoulder opposite your dominant hand. Your doctor will then use the needle to thread the pacemaker wires into the vein and to correctly place them in your heart.

An x-ray “movie” of the wires as they pass through your vein and into your heart will help your doctor place them. Once the wires are in place, your doctor will make a small cut into the skin of your chest or abdomen.

He or she will slip the pacemaker’s small metal box through the cut, place it just under your skin, and connect it to the wires that lead to your heart. The box contains the pacemaker’s battery and generator.

Once the pacemaker is in place, your doctor will test it to make sure it works properly. He or she will then sew up the cut. The entire surgery takes a few hours.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/during.html

What To Expect After Pacemaker Surgery

Expect to stay in the hospital overnight so your health care team can check your heartbeat and make sure your pacemaker is working well. You’ll likely have to arrange for a ride to and from the hospital because your doctor may not want you to drive yourself.

For a few days to weeks after surgery, you may have pain, swelling, or tenderness in the area where your pacemaker was placed. The pain usually is mild; over-the-counter medicines often can relieve it. Talk to your doctor before taking any pain medicines.

Your doctor may ask you to avoid vigorous activities and heavy lifting for about a month after pacemaker surgery. Most people return to their normal activities within a few days of having the surgery.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/after.html

How Will a Pacemaker Affect My Lifestyle?

Once you have a pacemaker, you have to avoid close or prolonged contact with electrical devices or devices that have strong magnetic fields. Devices that can interfere with a pacemaker include:

  • Cell phones and MP3 players (for example, iPods)
  • Household appliances, such as microwave ovens
  • High-tension wires
  • Metal detectors
  • Industrial welders
  • Electrical generators

These devices can disrupt the electrical signaling of your pacemaker and stop it from working properly. You may not be able to tell whether your pacemaker has been affected.

How likely a device is to disrupt your pacemaker depends on how long you’re exposed to it and how close it is to your pacemaker.

To be safe, some experts recommend not putting your cell phone or MP3 player in a shirt pocket over your pacemaker (if the devices are turned on).

You may want to hold your cell phone up to the ear that’s opposite the site where your pacemaker is implanted. If you strap your MP3 player to your arm while listening to it, put it on the arm that’s farther from your pacemaker.

You can still use household appliances, but avoid close and prolonged exposure, as it may interfere with your pacemaker.

You can walk through security system metal detectors at your normal pace. Security staff can check you with a metal detector wand as long as it isn’t held for too long over your pacemaker site. You should avoid sitting or standing close to a security system metal detector. Notify security staff if you have a pacemaker.

Also, stay at least 2 feet away from industrial welders and electrical generators.

Some medical procedures can disrupt your pacemaker. These procedures include:

  • Magnetic resonance imaging, or MRI
  • Shock-wave lithotripsy to get rid of kidney stones
  • Electrocauterization to stop bleeding during surgery

Let all of your doctors, dentists, and medical technicians know that you have a pacemaker. Your doctor can give you a card that states what kind of pacemaker you have. Carry this card in your wallet. You may want to wear a medical ID bracelet or necklace that states that you have a pacemaker.

Physical Activity

In most cases, having a pacemaker won’t limit you from doing sports and exercise, including strenuous activities.

You may need to avoid full-contact sports, such as football. Such contact could damage your pacemaker or shake loose the wires in your heart. Ask your doctor how much and what kinds of physical activity are safe for you.

Ongoing Care

Your doctor will want to check your pacemaker regularly (about every 3 months). Over time, a pacemaker can stop working properly because:

  • Its wires get dislodged or broken
  • Its battery gets weak or fails
  • Your heart disease progresses
  • Other devices have disrupted its electrical signaling

To check your pacemaker, your doctor may ask you to come in for an office visit several times a year. Some pacemaker functions can be checked remotely using a phone or the Internet.

Your doctor also may ask you to have an EKG (electrocardiogram) to check for changes in your heart’s electrical activity.

Battery Replacement

Pacemaker batteries last between 5 and 15 years (average 6 to 7 years), depending on how active the pacemaker is. Your doctor will replace the generator along with the battery before the battery starts to run down.

Replacing the generator and battery is less-involved surgery than the original surgery to implant the pacemaker. Your pacemaker wires also may need to be replaced eventually.

Your doctor can tell you whether your pacemaker or its wires need to be replaced when you see him or her for followup visits.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/lifestyle.html

Clinical Trial on Pace Makers

clinical trials related to pacemakers, talk with your doctor. You also can visit the following Web sites to learn more about clinical research and to search for clinical trials:

For more information about clinical trials for children, visit the NHLBI’s Children and Clinical Studies Web page.

SOURCE

http://www.nhlbi.nih.gov/health/health-topics/topics/pace/trials.html

RESOUCES on PaceMakers

Links to Other Information About Pacemakers

NHLBI Resources

Non-NHLBI Resources

Clinical Trials

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Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone

Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC

and

Reporter: Aviva Lev-Ari, PhD, RN

The Voice of  Justin Pearlman, MD, PhD, FACC

While working on angiogenesis imaging support at Harvard, the author discovered that injured heart muscle retains gadolinium-based contrast used for perfusion testing (1992). Whereas the gadolinium passes through normal tissue in less than 20 minutes and redistributes mostly to body fat, it stays where cell membranes are damaged, even if the damage is old. The gadolinium then “lights up” the damaged zone when normal heart muscle tissues appear dark by magnetic resonance imaging (MRI). Thus “scar mapping” was born. Prior to that discovery, the standard test for “viability” was a positron emission tomography (PET) scan reporting the presents of absence of normal sugar metabolism in damaged or ischemic heart muscle. PET relies on detection of a pair of gamma rays emitted by a radioactive label in a metabolite. The pair are emitted simultaneously at nearly 180 degrees apart, with a small angulation offset from the momentum of the emitter. The emission event requires a positron finds an electron, so it does not occur precisely where the metabolite sits, and thus has inherently a poor “resolution” (minimal distance where two distinct sources are identifiable as distinct).  The protocol for PET assessment of heart muscle viability utilized by the author and other investigators required intravenous infusion of glucose, insulin, and potassium, to assure good delivery of sugar to the healthy viable heart muscle, coupled to repeat blood tests to make sure the blood sugar and serum potassium levels were adequately maintained (otherwise the patient could suffer from low sugar or a potassium-related arrhythmia). Numerous investigatores followed up on this discovery, and determined that a gadolinium demarcated defect less than half the heart wall thickness corresponded clinically to viable myocardium (meaning one could expect improved function after revascularization of a blocked blood supply) whereas a defect more than half the wall thickness corresponded clinically to non-viable myocardium (no expected significant functional gain from revascularizing that region). Subsequently, a third option for assessment of viability was developed: combined PET and MRI.

PET/MRI device produced “high-quality cardiac MR imaging acquisitions,” overcoming any technical issues of having the PET detector within the MRI’s 3-tesla magnet field, Nensa and colleagues concluded.

“No negative side effects from the integrated imaging system design were observed,” they noted.

The researchers were able to show “a close match” between FDG-PET and MRI in assessing myocardial viability and infarct quantification among patients with acute and chronic myocardial infarction.

“These findings demonstrate the feasibility of clinical cardiac MR imaging with an integrated PET/MRI device,” they added. “However, to prove that the integrated design does not interfere with the performance of the device, a systematic intraindividual comparison with a comparable 3-tesla MRI system and identical sequence parameters is still needed.”

Future studies should investigate whether hybrid FDG-PET/MRI of myocardial infarction can provide additional information compared with MRI or PET alone, according to the authors.

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Study shows feasibility of cardiac PET/MRI — with caveats

By Wayne Forrest, AuntMinnie.com staff writer
May 9, 2013

Cardiac FDG-PET/MRI is feasible on an integrated whole-body PET/MRI system, but the hybrid modality still must prove it adds clinical relevance to cases of ischemic heart disease, according to a study published online May 7 in Radiology.

The study from University Hospital Essen in Germany found good concordance with the simultaneous acquisition of FDG-PET and MR images regarding both cine and late gadolinium-enhanced imaging in patients with myocardial infarction.

However, despite the simultaneous MRI and PET acquisition, “consolidated cardiac PET/MRI protocols need to be established, as long examination times associated with fasting seem to compromise patient compliance” with the exams, wrote lead author Dr. Felix Nensa, from the department of diagnostic and interventional radiology and neuroradiology, and colleaguesRadiology, May 7, 2013).

Cardiac feasibility study

The purpose of the study was to determine the feasibility of simultaneous acquisition of cardiac images on an integrated 3-tesla PET/MRI system, and to determine if the placement of the PET detector within the MRI’s field of magnet strength would adversely affect clinical results.

The researchers evaluated 20 consecutive patients with ischemic heart disease who were referred for FDG-PET/MRI between May and December 2012. Among the 20 patients, 14 had confirmed acute ST-elevation myocardial infarction within four to 15 days after interventional revascularization, one had suspected non-ST-elevation myocardial infarction, and five had chronic myocardial infarction.

Ten of the 20 patients underwent additional cardiac PET/CT before their PET/MRI scan.

Individuals with contraindications for gadolinium-based contrast agents and general MRI conditions, such as claustrophobia, were excluded from the study. All patients were asked to detail any personal discomfort or side effects that occurred during the PET/MRI exam.

All imaging studies were performed with an integrated whole-body PET/MRI system with 3-tesla field strength (Biograph mMR, Siemens Healthcare) and the PET insert inside the MRI scanner. All MRI sequences were performed with phased-array body surface coils designed for the PET/MRI system.

For late gadolinium-enhanced qualitative imaging, patients received gadobutrol (GadovistBayer HealthCare Pharmaceuticals) based on a dosage of 0.2 mmol/kg of body weight.

FDG-PET/MRI studies were performed after a fasting period of at least six hours, with FDG administered one hour before imaging with a mean of 202 (± 21) MBq. The scans began at a mean of 129 (± 41) minutes after FDG injection and included an electrocardiographically gated cardiac PET scan with one bed position and 3D image reconstruction.

For the FDG-PET/CT scans, an electrocardiographically gated cardiac PET/CT study was performed with a 128-slice CT unit (Biograph mCT, Siemens). PET scans began approximately 70 (± 12) minutes after FDG injection, with a mean of 211 (± 55) MBq.

Image comparisons

To compare the identification and characteristics of the infarcts between the two hybrid modalities, the researchers mapped the left ventricle with a 17-segment model, as recommended by the American Heart Association. Two-point scoring systems were used to assess myocardial tracer uptake, myocardial wall motion, and myocardial late enhancement in each segment.

In addition, the researchers measured the size of a patient’s infarct zone by drawing regions on the late gadolinium-enhanced MR images and PET images, and it was expressed as a percentage of the entire left ventricular myocardium.

Nensa and colleagues were able to complete 19 of 20 cardiac PET/MRI scans. One patient with ST-elevation myocardial infarction did not finish due to claustrophobia. Total PET/MRI scan time without patient preparation and positioning was 53 (± 3) minutes, and all cardiac MR images were rated as diagnostic in quality.

The analysis of FDG-PET and MRI with the 17-segment model found “good concordance” of the left ventricle with both cine imaging and late gadolinium-enhanced imaging in 18 of the 19 patients.

Of the 306 segments evaluated, 97 (32%) were rated as infarcted on PET images, compared with 93 (30%) rated as infarcted on late gadolinium-enhanced images and 90 (29%) on cine images.

Two-chamber views show “stunned myocardium” in a 66-year-old patient with ST-elevation myocardial infarction and acute occlusion of the left anterior descending artery. Cardiac PET/MRI was performed seven days after intervention. Late gadolinium-enhanced image (top left) shows no infarction zone. Fused late gadolinium-enhanced and PET images (top right) show that tracer uptake was reduced in segments 13-15 and 17. T2-weighted MR image (bottom left) shows myocardial edema (arrows) that corresponded well with the area of reduced tracer uptake on the bottom right image. All images courtesy of Radiology.

The size of the infarct zones averaged 22% of the entire left ventricular myocardium on PET images, compared with an average of 20% on late gadolinium-enhanced images.

Among the subgroup of 10 patients with an additional PET/CT scan, no significant difference in myocardial tracer uptake between PET/CT and PET/MR images was found.

In patient exit interviews, 16 patients cited long examination times (including patient preparation) as a source of discomfort. In addition, 11 patients cited the PET/MRI exam itself, i.e., noise, narrowness, and immobility, while 15 patients did not like having to fast.

Final conclusions

In summary, the PET/MRI device produced “high-quality cardiac MR imaging acquisitions,” overcoming any technical issues of having the PET detector within the MRI’s 3-tesla magnet field, Nensa and colleagues concluded.

“No negative side effects from the integrated imaging system design were observed,” they noted.

The researchers were able to show “a close match” between FDG-PET and MRI in assessing myocardial viability and infarct quantification among patients with acute and chronic myocardial infarction.

“These findings demonstrate the feasibility of clinical cardiac MR imaging with an integrated PET/MRI device,” they added. “However, to prove that the integrated design does not interfere with the performance of the device, a systematic intraindividual comparison with a comparable 3-tesla MRI system and identical sequence parameters is still needed.”

Future studies should investigate whether hybrid FDG-PET/MRI of myocardial infarction can provide additional information compared with MRI or PET alone, according to the authors.

Related Reading

MRI motion correction improves PET/MR image quality, July 6, 2012

SNM: PET/MRI for myocardial perfusion feasible but challenging, June 11, 2012

SNM: Hybrid PET/MRI study among top 5 research papers, June 7, 2011

Copyright © 2013 AuntMinnie.com

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SNM: Hybrid PET/MRI study among top 5 research papers

By Wayne Forrest, AuntMinnie.com staff writer

June 7, 2011 — SAN ANTONIO – The first-ever study on the clinical use of PET/MRI and a breakthrough on the use of FDG-PET to detect fevers of unknown origin were among the top research papers outlined Monday at this week’s Society of Nuclear Medicine (SNM) annual meeting.

More than 1,000 papers were submitted for consideration and presentation at this year’s meeting, with many studies showing how molecular imaging is gaining influence in the early detection of Alzheimer’s disease. Other submissions included a first-of-its-kind study on the use of near-infrared fluorescence and a new synthesized imaging agent to discover hidden blood clots in veins and arteries.

Hybrid PET/MRI

Early results from the clinical use of PET/MRI indicate that the hybrid modality can provide important diagnostic information about soft tissues and physiological functions throughout a patient’s body. The technology’s ability to find suspicious lesions and potential cancer already appears comparable to that of conventional molecular imaging methods.

In a German study, 11 patients with cancer underwent single-injection PET/CT followed by PET/MRI (Biograph mMR, Siemens Healthcare). Simultaneous PET/MRI acquisition was feasible and offered good-quality PET and MRI diagnostic data.

The analysis found that all 13 lesions detected at PET/CT were also identified by PET/MRI, with no significant difference between PET/CT and PET/MRI regarding the uptake ratios.

The study “demonstrates for the first time that newly introduced integrated whole-body MR/PET technology allows simultaneous acquisition of high-quality MR and PET data in a clinical setting within an acceptable time frame,” wrote lead study author Dr. Alexander Drzezga from TU München.

The hybrid technology could result in the development of new imaging agents that combine the diagnostic prowess of PET and MRI, Drzezga said. With the ability to image physiologic and pathophysiologic processes at the same time, the technology could open a new imaging discipline within nuclear medicine.

Carcinoma is compared in a patient who received a PET/CT scan 80 minutes after contrast injection (above), followed by a PET/MRI scan 160 minutes after contrast injection (below). All images courtesy of SNM.

FDG-PET and fever of unknown origin

Japanese researchers broke new ground in their study, which concluded that FDG-PET provided additional diagnostic information in cases of fever of unknown origin. The use of FDG-PET also had a high clinical impact, especially among patients with infectious diseases.

The retrospective study evaluated 81 consecutive patients with fever of unknown origin. They underwent FDG-PET at six Japanese institutions between July 2006 and December 2007.

Results were divided into four groups for final diagnoses: infection, arthritis/vasculitis/autoimmune/collagen disease, tumor/granuloma, and other/unknown.

The analysis found that sensitivity was highest in the tumor/granuloma group at 100% (seven of seven cases), followed by infection at 89% (24 of 27 cases) and arthritis/vasculitis/autoimmune/collagen disease at 65% (11 of 17 cases). Sensitivity was 0% (zero of one case) in the other/unknown category. Overall sensitivity was 81% and overall specificity was 75%.

Additional information provided by FDG-PET was highest in the infection group, at 76% of the cases (22 of 29), followed by tumor/granuloma at 75% (six of eight), arthritis/vasculitis/autoimmune/collagen disease at 43% (nine of 21), and other/unknown at 23% (five of 22).

The other/unknown group showed a high specificity of 84% (16 of 19 cases) and accurately excluded active focal inflammatory diseases and malignancy.

Lead study author Dr. Kozuo Kubota, PhD, chief of nuclear medicine at the National Center for Global Health and Medicine in Tokyo, said that until now, conventional modalities have produced low imaging resolution and very poor detectability for the fever’s cause.

“If the CT scan, ultrasound, or other conventional imaging technique fails, it is very difficult to find ways to find the focus of the fever,” Kubota said. “If we use FDG-PET, we can scan from head to thigh in only one scan to detect where the truly active lesion is. FDG is very sensitive both for inflammation and the tumor.”

With the addition of FDG-PET, physicians discovered a graft infection in a 50-year-old male with kidney failure and fever of unknown origin, with high FDG uptake illustrating the malady.

“I view this [study] as extraordinary,” said Dr. Michael Graham, PhD, director of nuclear medicine at the University of Iowa, who announced the top five papers. “This is in a setting where modern medicine is unable to come up with the answer, even after weeks. In about an hour-and-a-half, an FDG-PET scan came up with the answer with excellent sensitivity. We don’t get it every single time, but if it weren’t done, it would be mysterious what the patient had. It would be treated with antibiotics and hope for the best.”

“This is a huge step forward and I think it will change how we approach this problem,” he said.

PET and Alzheimer’s detection

Three studies presented at SNM 2011 added to the growing evidence that PET is an effective method to detect Alzheimer’s disease in its early stages, and that it provides a pathway to future clinical screening and treatments.

One lead study author, Dr. Kevin Ong, research scientist at Austin Hospital in Heidelberg, Australia, said that amyloid imaging with PET scans can help ascertain the likelihood that individuals will deteriorate cognitively within a few years, enabling more efficient channeling of healthcare resources.

Molecular imaging of Alzheimer’s disease has focused on detecting and analyzing the formation of the protein beta amyloid in the brain, which researchers say is directly involved in the pathology of Alzheimer’s. The presence of significant amyloid buildup is also linked to more rapid memory decline and brain atrophy.

Increased amyloid is bad for cognition even in the healthy elderly, noted lead study author Michael Devous Sr., PhD, director of neuroimaging for the Alzheimer’s Disease Center at the University of Texas Southwestern Medical Center.

The three ongoing studies involve several years of research based on hundreds of participants ranging widely in age, cognitive ability, and stage of disease.

Collective results showed that amyloid plaques build up at an estimated rate of 2% to 3% per year, and they often are already present in healthy older individuals. Amyloid plaque was present in 12% of people in their 60s, 30% of those in their 70s, and 55% of those older than 80.

In one study, approximately 25% of subjects older than 60 had amyloid plaques.

For individuals who have already developed a measurable memory decline, a positive scan for amyloid is the most accurate predictor of progression to Alzheimer’s disease, said Dr. Christopher Rowe, a lead investigator for the Australian Imaging, Biomarkers, and Lifestyle study of aging and professor of nuclear medicine at Austin Hospital.

Amyloid imaging with PET scans, he added, will be an important new tool in the assessment of cognitive decline.

Several studies have used carbon-11-labeled Pittsburgh Compound B (C-11 PIB), a PET imaging agent that binds to beta amyloid in brain tissue, but two of the current studies are assessing the benefit of F-18 florbetaben and F-18 florbetapir, which are designed for routine clinical use.

Both F-18 florbetaben and F-18 florbetapir are showing promise as reliable predictors of progression to Alzheimer’s disease, and F-18 amyloid imaging agents are considered most likely to move into clinical practice in the near future, perhaps as soon as next year.

NIRF for blood clot detection

In another novel study at SNM 2011, researchers from Massachusetts General Hospital are using near-infrared fluorescence (NIRF) and a new synthesized imaging agent to detect blood clots inside elusive veins, often within the deep tissues of the thighs and pelvis.

The agent uses a biomarker that seeks out a peptide — called fibrin — that is actively involved in the formation of blood clots. Combined with NIRF, which uses light energy to gather information from cells and tissues, the technique could also be used for coronary arteries. The fibrin peptide agent (EP-2104R) has already been tested in phase II clinical trials.

Lead study author Dr. Tetsuya Hara, PhD, noted that the availability of a high-resolution fibrin sensor is important for two reasons: intravascular NIRF imaging of coronary-sized arteries is now possible, and coupling the fibrin peptide with this technique may allow researchers to study coronary artery plaques and stents, which could potentially help identify patients at increased risk of heart attack.

The researchers were able to successfully detect fibrin-rich deep vein thrombosis with both intravital fluorescence microscopy and noninvasive fluorescence molecular tomography, allowing information to be acquired about tissues by analyzing how light is absorbed and scattered.

By coupling the fibrin peptide agent with intravascular NIRF imaging, researchers can now study microthrombi on coronary artery plaques and coronary stents that are at high risk for thrombosis and vessel occlusion.

This advance could help clinicians predict potential heart attacks and other major cardiovascular events, potentially saving more patients’ lives.

Related Reading

SNM exceeds fundraising goal, June 6, 2011

SNM: PET/MRI must prove its worth to ensure clinical adoption, June 6, 2011

PET/CT with NaF bone agent takes SNM’s Image of the Year, June 6, 2011

SNM proposes name change, May 3, 2011

SNM’s Clinical Trials Network: Progress despite growing pains, April 29, 2011

SOURCE:

http://www.auntminnie.com/index.aspx?sec=sup&sub=mol&pag=dis&ItemID=95494

Copyright © 2011 AuntMinnie.com

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Sudden Cardiac Death invisible at Autopsy: Forensic Power of Postmortem MRI

Aviva Lev-Ari, PhD, RN 4/18/2013

https://pharmaceuticalintelligence.com/2013/04/18/sudden-cardiac-death-invisible-at-autopsy-forensic-power-of-postmortem-mri/

Hypervascular Hepatocellular Carcinoma: Important clues from Gadoxetic acid-based MRI imaging

Ritu Saxena, PhD 4/10/2013

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Tilda Barliya PhD 10/17/2012

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MRI Cortical Thickness Biomarker Predicts AD-like CSF and Cognitive Decline in Normal Adults

Aviva Lev-Ari, PhD, RN 7/18/2012

https://pharmaceuticalintelligence.com/2012/07/18/mri-cortical-thickness-biomarker-predicts-ad-like-csf-and-cognitive-decline-in-normal-adults/

Early Detection of Prostate Cancer: American Urological Association (AUA) Guideline

Dror Nir, PhD 5/21/2013

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 Whole-body imaging as cancer screening tool; answering an unmet clinical need?

Dror Nir, PhD 1/3/2013

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Reporter: Aviva Lev-Ari, PhD, RN

 

Postmortem MRI shows sudden cardiac death invisible at autopsy

By Eric Barnes, AuntMinnie.com staff writer
April 17, 2013

In results that add substantial forensic power to identifying the cause of death, postmortem cardiac 3-tesla MRI has been found to identify sudden cardiac death in cases that are invisible at conventional autopsy, according to new research published online in the Journal of the American College of Cardiology.

In 76 cases, unenhanced MRI was able to visualize and discriminate 124 myocardial lesions, and there was excellent correlation among autopsy findings on chronic, subacute, and acute cases at MRI, the study authors said.

Thus, 3-tesla MRI can visualize chronic, subacute, and acute myocardial infarction in situ, and shows a possible source for sudden cardiac death in peracute infarction, wrote Dr. Christian Jackowski from the University of Bern in Switzerland, along with colleagues from the University of Lausanne in Switzerland and Linköping University in Sweden.

In particular, peracute infarction findings cannot be replicated in a physical autopsy; therefore, the study findings supports the use of forensic autopsy by permitting targeted histology, the group reported. Thus, MRI may serve as an alternative postmortem examination technique to traditional autopsy, Jackowski and colleagues wrote (JACC, April 3, 2013).

“In forensics, the cases can be solved better and more convincingly,” Jackowski wrote in an email to AuntMinnie.com. “The second impact I see is for clinical pathology, which has suffered from declining autopsy rates for decades now. I don’t expect the clinical autopsy numbers to increase again, so postmortem MRI can provide information about the cause of death, especially in patients that do not undergo a clinical autopsy anymore.”

Most cardiac deaths remain unsolved

Considering that cardiac events account for most deaths, postmortem MRI’s ability to demonstrate the cause of death in the heart has an enormous potential benefit, the group wrote, noting that “tissue alterations occurring during and after myocardial ischemia” are the most important — yet the least understood — issue with regard to conventional autopsy.

In previous small studies, acute, subacute, and chronic infarction have been differentiated based on signal behavior in T1- and T2-weighted images. Previous research has also suggested that unenhanced T2-weighted images without a hyperintense margin may represent acute ischemic lesions, which are aged between about 15 minutes and one hour, the group noted. Generally, though, cases of sudden cardiac death without myocardial findings of fresh thrombus have puzzled examiners and pathologists for decades.

The study sought to validate previous findings using postmortem MRI at 1.5 tesla, and also sought to use a larger study population. A secondary goal was to link the MRI finding of T2-weighted myocardial hypointensity to the possible myocardial appearance of sudden death to the patient’s coronary status at autopsy. The group used 3-tesla MRI to examine 136 corpses whose case histories showed chronic or acute cardiac anamnesis, or death from circumstances suggesting a cardiac origin.

All cases were examined with MRI using acquired short-axis and horizontal long-axis imaging on a 3-tesla MRI system (Achieva, Philips Healthcare) using a 16-channel torso coil.

Peracute myocardial infarction in postmortem MRI

Peracute myocardial infarction in postmortem MRI (death within one hour). A T2-weighted short-axis image presents with a local hypointensity within the lateral wall without hyperintense edematous margin. Autopsy of the specimen showed no visible alteration within the affected myocardium (not shown). Histology also failed to demonstrate ischemic alterations (not shown). Dissection of the coronary artery system revealed a fresh soft-plaque rupture with intimal hemorrhage within the circumflex coronary artery (not shown). Image courtesy of Dr. Christian Jackowski.

A total of 76 cases (62 men, 14 women; mean age at death 57.8 ± 16.7) presented with cardiac findings at postmortem MRI were investigated further.

Findings of cloudy hypointense myocardial areas in T2-weighted images without any hyperintense marginal edematous reaction were diagnosed as peracute ischemic lesions, and were not visible at autopsy, Jackowski and colleagues wrote.

Among the 76 cases, postmortem analysis identified 124 myocardial lesions (chronic = 25, subacute = 16, acute = 30, and peracute = 53), the team wrote. They found excellent correlation among myocardial findings at autopsy and chronic, subacute, and acute infarction cases. Peracute infarction areas detected at postmortem MRI were verified by histology in 62.3% of cases, and could be related to a matching coronary finding in 84.9%, they wrote.

In 15.1% of peracute lesions seen at MRI, the researchers found no matching coronary finding. But these patients presented severe myocardial hypertrophy or cocaine intoxication that “facilitated a finding of cardiac death without a verifiable coronary stenosis,” they noted.

Postmortem 3-tesla MRI revealed chronic, subacute, and myocardial infarction, the authors concluded, and in cases of peracute infarction, MRI pinpoints the possible source of sudden cardiac death, demonstrating affected myocardial areas at autopsy, Jackowski and colleagues wrote.

More precision in defining cardiac death

The study is the first to amass a large number of cases presenting with hypointense T2-weighted lesions that are well-correlated to coronary events; among the 42 cases, there were 53 hypointense T2-weighted lesions that remained invisible at macroscopic dissection, the authors wrote.

“Knowing about the postmortem MR finding allowed for a targeted histological examination that showed early ischemic alterations in 62.3% of lesions,” they wrote. “Based on the present study, it is … expected that ischemic alterations would have not been detected in a routine histological examination without having the MR finding in advance.”

At MRI, no histological alteration could be seen within the affected myocardium in 37.7% of the cases, the authors cautioned. On the other hand, a comparison of hypointensity in MRI to coronary status at autopsy showed findings that were able to explain an ischemic situation within the myocardium in 84.9% of the cases, demonstrating solid value for the postmortem imaging technique. In daily practice, this suggests that MRI could explain the majority of unsatisfactory autopsy cases thought to be sudden cardiac death but without verifiable myocardial changes.

Among the study limitations cited by the authors, the design did not permit the use of a control group, and the researchers were not blinded to the results, they stated, adding that the gold standard, autopsy, has several known limitations that hamper comparison with imaging.

Postmortem cardiac imaging comes with the disadvantage of no late enhancement. But it may be more than compensated for by the lack of cardiac motion or breathing artifacts.

Before this study, “we have seen hearts that presented with older or no ischemic lesions and may have three-vessel disease, but no fresh lesion that could explain why the heart stopped working exactly at that time,” Jackowski told AuntMinnie.com. “We then speak about sudden death, meaning that an arrhythmic event might have caused the death. However, what causes the arrhythmia often remains unclear. With postmortem MRI, we do see myocardial areas that the arrhythmia possibly originates from, areas that remain hidden for the human eye at autopsy. In forensics, the cases can be solved better and more convincingly.”

Related Reading

Advances in forensic imaging bring new opportunities for radiology, March 10, 2013

Elsevier launches forensic radiology journal, February 11, 2013

New society represents forensic radiology, November 29, 2011

High-field MRI appropriate for fetal autopsy, August 18, 2009
Copyright © 2013 AuntMinnie.com

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Minimally invasive image-guided therapy for inoperable hepatocellular carcinoma

Curator & Reporter: Dror Nir, PhD

Large organs like the liver are good candidates for focused treatment. The following paper:

Minimally invasive image-guided therapy for inoperable hepatocellular carcinoma: What is the evidence today?

By Beatrijs A. Seinstra1, et. al. published mid-2010, gives a review of the state-of-the-art of the then available methods for local lesions’ ablation. As far as ablation techniques availability, I have found this review very much relevant to today’s technological reality. It is worthwhile noting that in the last couple of years, new imaging-based navigation and guidance applications were introduced into the market holding a promise to improve the accuracy of administrating such treatment. These are subject to clinical validation in large clinical studies.  From the above mentioned publication I have chosen to highlight the parts discussing the importance of imaging-based guidance to the effective application of localized ablation-type therapies.

The clinical need:

Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Primary liver cancer is the sixth most common cancer worldwide with an incidence of 626,000 patients a year, and the third most common cause of cancer-related death [1]. Only 10–15% of HCC patients are suitable candidates for hepatic resection and liver transplantation due to the advanced stage of the disease at time of diagnosis and shortage of donors.

Immerging solution:

In order to provide therapeutic options for patients with inoperable HCC, several minimally invasive image-guided therapies for locoregional treatment have been developed. HCC has a tendency to remain confined to the liver until the disease has advanced, making these treatments particularly attractive.

Minimally invasive image-guided therapies can be divided into the group of the tumor ablative techniques or the group of image-guided catheter-based techniques. Tumor ablative techniques are either based on thermal tumor destruction, as in radiofrequency ablation (RFA), cryoablation, microwave ablation, laser ablation and high-intensity focused ultrasound (HIFU), or chemical tumor destruction, as in percutaneous ethanol injection (PEI). These techniques are mostly used for early stage disease. Image-guided catheter-based techniques rely on intra-arterial delivery of embolic, chemoembolic, or radioembolic agents [22]. These techniques enable treatment of large lesions or whole liver treatment, and are as such used for intermediate stage HCC (Figure 1).

Minimally invasive image-guided ablation techniques and intra-arterial interventions may prolong survival, spare more functioning liver tissue in comparison to surgical resection (which can be very important in cirrhotic patients), allow retreatment if necessary, and may be an effective bridge to transplantation [2327].

During the last 2 decades, minimally invasive image-guided therapies have revolutionized the management of inoperable HCC.

The value of image guidance

Accurate imaging is of great importance during minimally invasive loco-regional therapies to efficiently guide and monitor the treatment. It enables proper placement of instruments, like the probe in case of ablation or the catheter in case of intra-arterial therapy, and accurate monitoring of the progression of the necrotic zone during ablation.

can all be employed. In current clinical practice, placement of the catheter in intra-arterial procedures is usually performed under fluoroscopic guidance, while ablation may be guided by ultrasound, CT or MRI.

  • Ultrasound guidance allows probe insertion from every angle, offers real time visualization and correction for motion artifacts when targeting the tumor, and is low cost. However, the gas created during ablation (or ice in the case of cryoablation) hampers penetration of the ultrasound beams in tissue, causing acoustic shadowing and obscuring image details like the delineation between tumor borders and ablation zone.
  • CT is also frequently used to guide minimally invasive ablation therapy, and is a reliable modality to confirm treatment results. In comparison to US, it provides increased lesion discrimination, a more reliable depiction of ablated/non-ablated interfaces, and a better correlation to pathologic size [28]. However, due to its hypervascularity, small HCCs can only be clearly visualized in the arterial phase for a short period of time. Another disadvantage of CT is the exposure of the patient and physician to ionizing radiation.
  • Combining US imaging for probe placement and CT for ablation monitoring reduces this exposure. At the moment, hybrid systems are being developed, enabling combination of imaging techniques, like ultrasound and CT imaging, thereby improving the registration accuracy during treatment [29]. The interest in MRI-guided ablation is growing, as it produces a high-quality image allowing high-sensitivity tumor detection and accurate identification of the target region with multiplanar imaging.
  • MRI also enables real-time monitoring of the temperature evolution during treatment [3035]. However, MRI is an expensive technique, and MRI-guided ablation is still limited in clinical practice. Currently, the most widely used ablation technique for percutaneous treatment of focal hepatic malignancies is radiofrequency ablation (RFA), which has been shown to be safe and effective for the treatment of early stage HCC [4850]. During RFA, a small electrode is placed within the tumor, and a high-frequency alternating electric current (approximately 400 MHz) is generated, causing ionic agitation within the tissue. ….. Most frequently ultrasound is used for image guidance (Figs. 23), but there are reports of groups who use CT, MRI, or fluoroscopic imaging.
Ultrasound guided RFA. a: HCC lesion in a non-surgical patient pre-treatment (pointed out by arrow). b: Just after start treatment, electrode placed centrally in the tumor. c: Gas formation during ablation causes acoustic shadowing

Ultrasound guided RFA. a: HCC lesion in a non-surgical patient pre-treatment (pointed out by arrow). b: Just after start treatment, electrode placed centrally in the tumor. c: Gas formation during ablation causes acoustic shadowing

Contrast-enhanced CT pre- and post-RFA. Same patient as in Fig. 2. a: Hypervascular lesion (biopsy proven HCC) in right liver lobe (pointed out by arrow) before treatment. b: Ablated lesion directly post ablation, with reactive hyperemia around the RFA lesion

Contrast-enhanced CT pre- and post-RFA. Same patient as in Fig. 2. a: Hypervascular lesion (biopsy proven HCC) in right liver lobe (pointed out by arrow) before treatment. b: Ablated lesion directly post ablation, with reactive hyperemia around the RFA lesion

References

1.

Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108PubMedCrossRef

2.

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Reporter and Curator: Ritu Saxena, PhD

Magnetic Resonance Imaging (MRI) is increasingly used in clinical diagnostics, for a rapidly growing number of indications. The MRI technique is non-invasive and can provide information on the anatomy, function and metabolism of tissues in vivo (Strijkers GJ, et al, Anticancer Agents Med Chem, May 2007;7(3):291-305). Basic contrast in the MRI image scans is as a result of contrast generated by differences in the relaxation times between different regions. Since the intrinsic contrast generated between regions is limited to allow clear and specific diagnosis, MRI contrast agents administered intravenously are increasingly being used to alter image contrast.

Gadoxetic acid, a gadolinium-based compound, is a recently developed hepatobiliary-specific contrast material for MRI that has high sensitivity in the detection of malignant liver tumors. Its salt, gadoxetate disodium, is marketed as Primovist in Europe and Eovist in the United States by Bayer HealthCare Pharmaceuticals. Gadoxetic acid is taken up by hepatocytes and then excreted into the bile ducts (Schuhmann-Giampieri G, et al, Radiology, Apr 1992;183(1):59-64). Therefore, hepatic focal lesions without normal hepatobiliary function are depicted as hypointense areas compared with the well-enhanced hyperintense background liver in the hepatobiliary phase of gadoxetic acid–enhanced MR imaging. In addition, gadoxetic acid can be used in the same way as gadopentetate dimeglumine to evaluate the hemodynamics of hepatic lesions in the dynamic phase after an intravenous bolus injection (Kitao A, et al, Radiology, Sep 2010;256(3):817-26).

Recently, researchers from Kanazawa University Graduate School of Medical Science, (Kanazawa, Japan) analyzed the correlation among biologic features, tumor marker production, and signal intensity at gadoxetic acid-enhanced MR imaging in hepatocellular carcinomas (HCCs). The findings were published in Radiology journal. The research was supported in part by a Grant-in-Aid for Scientific Research (21591549) from the Ministry of Education, Culture, Sports, Science and Technology; and by Health and Labor Sciences Research Grants for “Development of novel molecular markers and imaging modalities for earlier diagnosis of hepatocellular carcinoma.”

Research significance: HCC is the most frequent primary malignant tumor of liver and is the third most common cause of cancer death worldwide. It is the most Hepatocellular.

The accurate detection and characterization of HCC focal lesions is crucial for improving prognosis of patients with HCC.

Research problem: Gadoxetic acid–enhanced MR imaging is highly accurate for diagnosing HCC lesions. As discussed earlier, in this imaging process, hepatic focal lesions without normal hepatobiliary are hypointense as compared with the well-enhanced hyperintense background liver. However, approximately 6%–15% of hypervascular HCCs demonstrate isointensity or hyperintensity (Kitao A, et al, Eur Radiol, Oct 2011;21(10):2056-66).

Hypothesis: The reason for hyperintensity in some HCC lesions was previously shown to be due to overexpression of organic anion transporting polypeptide 8 (OATP8) (Kitao A, et al, Radiology, Sep 2010;256(3):817-26). The authors speculated that there might be a correlation of the tumor marker production and signal intensity (SI) on hepatobiliary phase images, which would reflect distinct genomic and proteomic expression of HCC. Thus, authors stated that “the purpose of this study was to analyze the correlation among the pathologic and biologic features, tumor marker production, with signal intensity (SI) on hepatobiliary phase gadoxetic acid–enhanced MR images of HCC” (Kitao A, et al, Radiology, Dec 2012;265(3):780-9).

Experimental design: From April 2008 to September 2011, 180 surgically resected HCCs in 180 patients (age, 65.0 years ± 10.3 [range, 34–83 years]; 138 men, 42 women) were classified as either hypointense (n = 158) or hyperintense (n = 22) compared with the signal intensity of the background liver on hepatobiliary phase gadoxetic acid–enhanced MR images (Abstract of the study).

Pathologic features were analyzed.

Serum analysis and immunohistochemical staining was performed and following were compared:

  1. Alpha fetoprotein (AFP) – is a main tumor marker of HCCs. AFP is the most abundant plasma protein found in the human fetus and plasma levels decrease rapidly after birth. A level above 500 nanograms/milliliter of AFP in adults can be indicative of hepatocellular carcinoma, germ cell tumors, and metastatic cancers of the liver.
  2. Absence of protein induced by vitamin K or antagonist-II (PIVKA-II) – is a clinically important serum tumor marker. PIVKAII is an incomplete coagulation factor prothrombin II whose production is related to the absence of vitamin K or the presence of the antagonist of vitamin K, which is the cofactor of g carboxylase that converts precursor into prothrombin.

Serum levels of both AFP and PIVKA-II correlate with HCC malignancy and prognosis (Miyaaki H, et al, J Gastroenterol, Dec 2007;42(12):962-8).

Results: The hyperintense HCCs showed significantly higher differentiation grade than the hypointense HCCs (P = .028). There was a significant difference in the proliferation pattern between the hypointense and hyperintense HCCs (P < .001) and the hyperintense HCCs showed a significantly lower rate of portal vein invasion than that of hypointense HCCs (P = .039). The serum levels of tumor markers AFP, AFP-L3, and PIVKA-II were significantly lower in the patients with hyperintense HCCs than in those with

hypointense HCCs (P = .003, .004, and .026). In addition, immunohistochemical analysis revealed that the expression of FP and PIVKA-II was lower in hyperintense than in hypointense HCCs (both P < .001). Also, hyperintense HCCs showed lower recurrence rate than hypointense HCCs (P = .039).

Conclusion: Variation was observed within differently stained lesions of HCC in the hepatobiliary phase gadoxetic acid–enhanced MR images as evident in tumor marker expression, proliferation pattern, differentiation grade, immunohistochemical analysis and recurrence.  The results lead to the hypothesis that hyperintense HCCs in the hepatobiliary phase gadoxetic acid–enhanced MR images might represent a particular type of HCC that is hypervascular and biologically less aggressive as compared to hypovascular HCCs. Interestingly, this research is another great example where tumor heterogeneity has been brought to light (similar to genetic heterogeneity in triple negative breast cancer deciphered by Lehmann BD, et al, 2011). The heterogeneity might be the basis of answers to why a particular therapy fails in a certain tumor type and fortifying evidence for appropriate analysis of the tumor for obtaining the desired tumor response from a particular drug.

Reference:

Kitao A, et al, Radiology, Dec 2012;265(3):780-9

Strijkers GJ, et al, Anticancer Agents Med Chem, May 2007;7(3):291-305

Schuhmann-Giampieri G, et al, Radiology, Apr 1992;183(1):59-64

Kitao A, et al, Radiology, Sep 2010;256(3):817-26

Kitao A, et al, Eur Radiol, Oct 2011;21(10):2056-66

Kitao A, et al, Radiology, Sep 2010;256(3):817-26

Miyaaki H, et al, J Gastroenterol, Dec 2007;42(12):962-8

Lehmann BD, et al, J Clin Invest, 2011;121(7):2750–2767

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