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Posts Tagged ‘Magnetic resonance imaging’


Author and Curator: Dror Nir, PhD

 

This post is a continuation of

Imaging: seeing or imagining? (Part 1)

https://pharmaceuticalintelligence.com/2012/09/10/imaging-seeing-or-imagining-part-1/

 

That is the question…

Anyone who follows healthcare news, as I do , cannot help being impressed with the number of scientific and non-scientific items that mention the applicability of Magnetic Resonance Imaging (‘MRI’) to medical procedures.

A very important aspect that is worthwhile noting is that the promise MRI bears to improve patients’ screening – pre-clinical diagnosis, better treatment choice, treatment guidance and outcome follow-up – is based on new techniques that enables MRI-based tissue characterisation.

Magnetic resonance imaging (MRI) is an imaging device that relies on the well-known physical phenomena named “Nuclear Magnetic Resonance”. It so happens that, due to its short relaxation time, the 1H isotope (spin ½ nucleus) has a very distinctive response to changes in the surrounding magnetic field. This serves MRI imaging of the human body well as, basically, we are 90% water. The MRI device makes use of strong magnetic fields changing at radio frequency to produce cross-sectional images of organs and internal structures in the body. Because the signal detected by an MRI machine varies depending on the water content and local magnetic properties of a particular area of the body, different tissues or substances can be distinguished from one another in the scan’s resulting image.

MRI scan of a breast lesion (Source Radiology.com)

The main advantages of MRI in comparison to X-ray-based devices such as CT scanners and mammography systems are that the energy it uses is non-ionizing and it can differentiate soft tissues very well based on differences in their water content.

In the last decade, the basic imaging capabilities of MRI have been augmented for the purpose of cancer patient management, by using magnetically active materials (called contrast agents) and adding functional measurements such as tissue temperature to show internal structures or abnormalities more clearly.

In order to increase the specificity and sensitivity of MRI imaging in cancer detection, various imaging strategies have been developed. The most discussed in MRI related literature are:

  • T2 weighted imaging: The measured response of the 1H isotope in a resolution cell of a T2-weighted image is related to the extent of random tumbling and the rotational motion of the water molecules within that resolution cell. The faster the rotation of the water molecule, the higher the measured value of the T2 weighted response in that resolution cell. For example, prostate cancer is characterized by a low T2 response relative to the values typical to normal prostatic tissue [5].

T2 MRI pelvis with Endo Rectal Coil ( DATA of Dr. Lance Mynders, MAYO Clinic)

  • Dynamic Contrast Enhanced (DCE) MRI involves a series of rapid MRI scans in the presence of a contrast agent. In the case of scanning the prostate, the most commonly used material is gadolinium [4].

Axial MRI Lava DCE with Endo Rectal ( DATA of Dr. Lance Mynders, MAYO Clinic)

  • Diffusion weighted (DW) imaging: Provides an image intensity that is related to the microscopic motion of water molecules [5].

DW image of the left parietal glioblastoma multiforme (WHO grade IV) in a 59-year-old woman, Al-Okaili R N et al. Radiographics 2006;26:S173-S189

  • Multifunctional MRI: MRI image overlaid with combined information from T2-weighted scans, dynamic contrast-enhancement (DCE), and diffusion weighting (DW) [5].
  • Blood oxygen level-dependent (BOLD) MRI: Assessing tissue oxygenation. Tumors are characterized by a higher density of micro blood vessels. The images that are acquired follow changes in the concentration of paramagnetic deoxyhaemoglobin [5].

In the last couple of years, medical opinion leaders are offering to use MRI to solve almost every weakness of the cancer patients’ pathway. Such proposals are not always supported by any evidence of feasibility. For example, a couple of weeks ago, the British Medical Journal published a study [1] concluding that women carrying a mutation in the BRCA1 or BRCA2 genes who have undergone a mammogram or chest x-ray before the age of 30 are more likely to develop breast cancer than those who carry the gene mutation but who have not been exposed to mammography. What is published over the internet and media to patients and lay medical practitioners is: “The results of this study support the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging) as the main tool for surveillance in young women with BRCA1/2 mutations.”.

Why is ultrasound not mentioned as a potential “non-ionising radiation imaging technique”?

Another illustration is the following advert:

Advert in favour of MRI termal imaging of breast

An MRI scan takes between 30 to 45 minutes to perform (not including the time of waiting for the interpretation by the radiologist). It requires the support of around 4 well-trained team members. It costs between $400 and $3500 (depending on the scan).

The important question, therefore, is: Are there, in the USA, enough MRI  systems to meet the demand of 40 million scans a year addressing women with radiographically dense  breasts? Toda there are approximately 10,000 MRI systems in the USA. Only a small percentage (~2%) of the examinations are related to breast cancer. A

A rough calculation reveals that around 10,000 additional MRI centers would need to be financed and operated to meet that demand alone.

References

  1. Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK), BMJ 2012; 345 doi: 10.1136/bmj.e5660 (Published 6 September 2012), Cite this as: BMJ 2012;345:e5660 – http://www.bmj.com/content/345/bmj.e5660
  1. http://www.auntminnieeurope.com/index.aspx?sec=sup&sub=wom&pag=dis&itemId=607075
  1. Ahmed HU, Kirkham A, Arya M, Illing R, Freeman A, Allen C, Emberton M. Is it time to consider a role for MRI before prostate biopsy? Nat Rev Clin Oncol. 2009;6(4):197-206.
  1. Puech P, Potiron E, Lemaitre L, Leroy X, Haber GP, Crouzet S, Kamoi K, Villers A. Dynamic contrast-enhanced-magnetic resonance imaging evaluation of intraprostatic prostate cancer: correlation with radical prostatectomy specimens. Urology. 2009;74(5):1094-9.
  1. Advanced MR Imaging Techniques in the Diagnosis of Intraaxial Brain Tumors in Adults, Al-Okaili R N et al. Radiographics 2006;26:S173-S189 ,

http://radiographics.rsna.org/content/26/suppl_1/S173.full

  1. Ahmed HU. The Index Lesion and the Origin of Prostate Cancer. N Engl J Med. 2009 Oct; 361(17): 1704-6

Writer: Dror Nir, PhD.

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The Incentive for “Imaging based cancer patient’ management”


Author and Curator: Dror Nir, PhD

It is generally agreed by radiologists and oncologists that in order to provide a comprehensive work-flow that complies with the principles of personalized medicine, future cancer patients’ management will heavily rely on “smart imaging” applications. These could be accompanied by highly sensitive and specific bio-markers, which are expected to be delivered by pharmaceutical companies in the upcoming decade. In the context of this post, smart imaging refers to imaging systems that are enhanced with tissue characterization and computerized image interpretation applications. It is expected that such systems will enable gathering of comprehensive clinical information on cancer tumors, such as location, size and rate of growth.

What is the main incentive for promoting cancer patients’ management based on smart imaging? 

It promises to enable personalized cancer patient management by providing the medical practitioner with a non-invasive and non-destructive tool to detect, stage and follow up cancer tumors in a standardized and reproducible manner. Furthermore, applying smart imaging that provides valuable disease-related information throughout the management pathway of cancer patient will eventually result in reducing the growing burden of health-care costs related to cancer patients’ treatment.

Let’s briefly review the segments that are common to all cancer patients’ pathway: screening, treatment and costs.

 

Screening for cancer: It is well known that one of the important factors in cancer treatment success is the specific disease staging. Often this is dependent on when the patient is diagnosed as a cancer patient. In order to detect cancer as early as possible, i.e. before any symptoms appear, leaders in cancer patients’ management came up with the idea of screening. To date, two screening programs are the most spoken of: the “officially approved and budgeted” breast cancer screening; and the unofficial, but still extremely costly, prostate cancer screening. After 20 years of practice, both are causing serious controversies:

In trend analysis of WHO mortality data base [1], the authors, Autier P, Boniol M, Gavin A and Vatten LJ, argue that breast cancer mortality in neighboring European countries with different levels of screening but similar access to treatment is the same: “The contrast between the time differences in implementation of mammography screening and the similarity in reductions in mortality between the country pairs suggest that screening did not play a direct part in the reductions in breast cancer mortality”.

In prostate cancer mortality at 11 years of follow-up [2],  the authors,Schröder FH et. al. argue regarding prostate cancer patients’ overdiagnosis and overtreatment: “To prevent one death from prostate cancer at 11 years of follow-up, 1055 men would need to be invited for screening and 37 cancers would need to be detected”.

The lobbying campaign (see picture below)  that AdmeTech (http://www.admetech.org/) is conducting in order to raise the USA administration’s awareness and get funding to improve prostate cancer treatment is a tribute to patients’ and practitioners’ frustration.

 

 

 

Treatment: Current state of the art in oncology is characterized by a shift in  the decision-making process from an evidence-based guidelines approach toward personalized medicine. Information gathered from large clinical trials with regard to individual biological cancer characteristics leads to a more comprehensive understanding of cancer.

Quoting from the National cancer institute (http://www.cancer.gov/) website: “Advances accrued over the past decade of cancer research have fundamentally changed the conversations that Americans can have about cancer. Although many still think of a single disease affecting different parts of the body, research tells us through new tools and technologies, massive computing power, and new insights from other fields that cancer is, in fact, a collection of many diseases whose ultimate number, causes, and treatment represent a challenging biomedical puzzle. Yet cancer’s complexity also provides a range of opportunities to confront its many incarnations”.

Personalized medicine, whether it uses cytostatics, hormones, growth inhibitors, monoclonal antibodies, and loco-regional medical devices, proves more efficient, less toxic, less expensive, and creates new opportunities for cancer patients and health care providers, including the medical industry.

To date, at least 50 types of systemic oncological treatments can be offered with much more quality and efficiency through patient selection and treatment outcome prediction.

Figure taken from presentation given by Prof. Jaak Janssens at the INTERVENTIONAL ONCOLOGY SOCIETY meeting held in Brussels in October 2011

For oncologists, recent technological developments in medical imaging-guided tissue acquisition technology (biopsy) create opportunities to provide representative fresh biological materials in a large enough quantity for all kinds of diagnostic tests.

 

Health-care economics: We are living in an era where life expectancy is increasing while national treasuries are over their limits in supporting health care costs. In the USA, of the nation’s 10 most expensive medical conditions, cancer has the highest cost per person. The total cost of treating cancer in the U.S. rose from about $95.5 billion in 2000 to $124.6 billion in 2010, the National Cancer Institute (www.camcer.gov) estimates. The true sum is probably higher as this estimate is based on average costs from 2001-2006, before many expensive treatments came out; quoting from www.usatoday.com : “new drugs often cost $100,000 or more a year. Patients are being put on them sooner in the course of their illness and for a longer time, sometimes for the rest of their lives.”

With such high costs at stake, solutions to reduce the overall cost of cancer patients’ management should be considered. My experience is that introducing smart imaging applications into routine use could contribute to significant savings in the overall cost of cancer patients’ management, by enabling personalized treatment choice and timely monitoring of tumors’ response to treatment.

 

 References

  1. 1.      BMJ. 2011 Jul 28;343:d4411. doi: 10.1136/bmj.d4411
  2. 2.      (N Engl J Med. 2012 Mar 15;366(11):981-90):

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Reporter: Aviva Lev-Ari, PhD, RN

MRI cortical thickness biomarker predicts AD-like CSF and cognitive decline in normal adults

Bradford C. Dickerson, MD and David A. Wolk, MD On behalf of the Alzheimer’s Disease Neuroimaging Initiative

Author Affiliations

From the Frontotemporal Dementia Unit, Department of Neurology, Massachusetts Alzheimer’s Disease Research Center, and Athinoula A. Martinos Center for Biomedical Imaging (B.C.D.), Massachusetts General Hospital and Harvard Medical School, Boston; and Department of Neurology, Alzheimer’s Disease Core Center, and Penn Memory Center (D.A.W.), University of Pennsylvania, Philadelphia.

Correspondence & reprint requests to Dr. Dickerson: bradd@nmr.mgh.harvard.edu

ABSTRACT

Objective: New preclinical Alzheimer disease (AD) diagnostic criteria have been developed using biomarkers in cognitively normal (CN) adults. We implemented these criteria using an MRI biomarker previously associated with AD dementia, testing the hypothesis that individuals at high risk for preclinical AD would be at elevated risk for cognitive decline.

Methods: The Alzheimer’s Disease Neuroimaging Initiative database was interrogated for CN individuals. MRI data were processed using a published set of a priori regions of interest to derive a single measure known as the AD signature (ADsig). Each individual was classified as ADsig-low (≥1 SD below the mean: high risk for preclinical AD), ADsig-average (within 1 SD of mean), or ADsig-high (≥1 SD above mean). A 3-year cognitive decline outcome was defined a priori using change in Clinical Dementia Rating sum of boxes and selected neuropsychological measures.

Results: Individuals at high risk for preclinical AD were more likely to experience cognitive decline, which developed in 21% compared with 7% of ADsig-average and 0% of ADsig-high groups (p = 0.03). Logistic regression demonstrated that every 1 SD of cortical thinning was associated with a nearly tripled risk of cognitive decline (p = 0.02). Of those for whom baseline CSF data were available, 60% of the high risk for preclinical AD group had CSF characteristics consistent with AD while 36% of the ADsig-average and 19% of the ADsig-high groups had such CSF characteristics (p = 0.1).

Conclusions: This approach to the detection of individuals at high risk for preclinical AD—identified in single CN individuals using this quantitative ADsig MRI biomarker—may provide investigators with a population enriched for AD pathobiology and with a relatively high likelihood of imminent cognitive decline consistent with prodromal AD.

 

Copyright © 2011 by AAN Enterprises, Inc.

http://www.neurology.org/content/early/2011/12/21/WNL.0b013e31823efc6c.abstract

 

 

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