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Introducing smart-imaging into radiologists’ daily practice.

Posted in Imaging-based Cancer Patient Management, tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , on October 9, 2012| 6 Comments »

Introducing smart-imaging into radiologists’ daily practice.

Author and Curator: Dror Nir, PhD

Article 11.3.1 Introducing smart imaging into radiologists daily practice

Radiology congresses are all about imaging in medicine. Interestingly, radiology originates from radiation. It was the discovery of X-ray radiation at the beginning of the 20th century that opened the road to “seeing” the inside of the human body without harming it (at that time that meant cutting into the body).

Radiology meetings are about sharing experience and knowhow on imaging-based management patients. The main topic is always image-interpretation: the bottom line of clinical radiology! This year’s European Congress of Radiology (ECR) dedicated few of its sessions to recent developments in image-interpretation tools. I chose to discuss the one that I consider contributing the most to the future of cancer patients’ management.

In the refresher course dedicated to computer application the discussion was aimed at understanding the question “How do image processing and CAD impact radiological daily practice?” Experts’ reviews gave the audience some background information on the following subjects:

  1. A.     The link between image reconstruction and image analysis.
  2. B.     Semantic web technologies for sharing and reusing imaging-related information
  3. C.     Image processing and CAD: workflow in clinical practice.

I find item A to be a fundamental education item. Not once did I hear a radiologist saying: “I know this is the lesion because it’s different on the image”.  Being aware of the computational concepts behind image rendering, even if it is at a very high level and lacking deep understanding of the computational processes,  will contribute to more balanced interpretations.

Item B is addressing the dream of investigators worldwide. Imagine that we could perform a web search and find educating, curated materials linking visuals and related clinical information, including standardized pathology reporting. We would only need to remember that search engines used certain search methods and agree, worldwide, on the method and language to be used when describing things. Having such tools is a pre-requisite to successful pharmaceutical and bio-tech development.

I find item C strongly linked to A, as all methods for better image interpretation must fit into a workflow. This is a design goal that is not trivial to achieve. To understand what I mean by that, try to think about how you could integrate the following examples in your daily workflow: i.e. what kind of expertise is needed for execution, how much time it will take, do you have the infrastructure?

In the rest of this post, I would like to highlight, through examples that were discussed during ECR 2012, the aspect of improving cancer patients’ clinical assessment by using information fusion to support better image interpretation.

  • Adding up quantitative information from MR spectroscopy (quantifies biochemical property of a target lesion) and Dynamic Contrast Enhanced MR imaging (highlights lesion vasculature).

Image provided by: Dr. Pascal Baltzer, director of mammography at the centre for radiology at Friedrich Schiller University in Jena, Germany

 
  • Registration of images generated by different imaging modalities (Multi-modal imaging registration).

The following examples: Fig 2 demonstrates registration of a mammography image of a breast lesion to an MRI image of this lesion. Fig3 demonstrates registration of an ultrasound image of a breast lesion scanned by an Automatic Breast Ultrasound (ABUS) system and an MRI image of the same lesion.

Images provided by members of the HAMAM project (an EU, FP7 funded research project: Highly Accurate Breast Cancer Diagnosis through Integration of Biological Knowledge, Novel Imaging Modalities, and Modelling): http://www.hamam-project.org

 

 Multi-modality image registration is usually based on the alignment of image-features apparent in the scanned regions. For ABUS-MRI matching these were: the location of the nipple and the breast thickness; the posterior of the nipple in both modalities; the medial-lateral distance of the nipple to the breast edge on ultrasound; and an approximation of the rib­cage using a cylinder on the MRI. A mean accuracy of 14mm was achieved.

Also from the HAMAM project, registration of ABUS image to a mammography image:

registration of ABUS image to a mammography image, Image provided by members of the HAMAM project (an EU, FP7 funded research project: Highly Accurate Breast Cancer Diagnosis through Integration of Biological Knowledge, Novel Imaging Modalities, and Modelling): http://www.hamam-project.org

  • Automatic segmentation of suspicious regions of interest seen in breast MRI images

Segmentation of suspicious the lesions on the image is the preliminary step in tumor evaluation; e.g. finding its size and location. Since lesions have different signal/image character­istics to the rest of the breast tissue, it gives hope for the development of computerized segmentation techniques. If successful, such techniques bear the promise of enhancing standardization in the reporting of lesions size and location: Very important information for the success of the treatment step.

Roberta Fusco of the National Cancer Institute of Naples Pascal Foundation, Naples/IT suggested the following automatic method for suspi­cious ROI selection within the breast using dynamic-derived information from DCE-MRI data.

 

Automatic segmentation of suspicious ROI in breast MRI images, image provided by Roberta Fusco of the National Cancer Institute of Naples Pascal Foundation, Naples/IT

 

 Her algorithm includes three steps (Figure 2): (i) breast mask extraction by means of automatic intensity threshold estimation (Otsu Thresh-holding) on the par­ametric map obtained through the sum of intensity differences (SOD) calculated pixel by pixel; (ii) hole-filling and leakage repair by means of morphological operators: closing is required to fill the holes on the boundaries of breast mask, filling is required to fill the holes within the breasts, erosion is required to reduce the dilation obtained by the closing operation; (iii) suspicious ROIs extraction: a pixel is assigned to a suspicious ROI if it satisfies two conditions: the maximum of its normalized time-intensity curve should be greater than 0.3 and the maximum signal intensity should be reached before the end of the scan time. The first condition assures that the pixels within the ROI have a significant contrast agent uptake (thus excluding type I and type II curves) and the second condition is required for the time-intensity pattern to be of type IV or V (thus excluding type III curves).

Written by: Dror Nir, PhD

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Imaging-guided biopsies: Is there a preferred strategy to choose?

Posted in Bio Instrumentation in Experimental Life Sciences Research, CANCER BIOLOGY & Innovations in Cancer Therapy, Imaging-based Cancer Patient Management, Medical Devices R&D Investment, tagged , , , , , , , , , , , , , , , , , , , , , , , on September 29, 2012| 7 Comments »

Imaging-guided biopsies: Is there a preferred strategy to choose?

Author: Dror Nir, PhD

Article 11.3.3 Imaging guided biopsies Is there a preferred strategy to choose

The most stressful period in a cancer patients’ pathway is from the moment they fail a screening test or present with suspicious symptoms to the moment they are diagnosed. Today’s medical guidelines require histopathology findings as the only acceptable proof: positive results  mean you are a cancer patient, negative results mean, well…maybe you are and maybe you are not. You now enter into what might be a very long period, sometime years, of uncertainty regarding your health and prospects. And why?

Because the substance for histopathology is acquired by biopsies, and biopsies are known to be inaccurate. For example, breast and prostate biopsies  fail to find 25% to 35% of the cancer lesions at the first biopsy session.

Therefore, it is not surprising that from the beginning of this procedure,  medical practitioners look for ways to incorporate imaging into the workflow. In the last decade, significant progress has been made in the introduction of imaging-guided biopsies. The most common modalities were ultrasound and CT/mammography. Recently, as the industry solved the issues of magnetic field compatibility for biopsy needles and the introduction of open MRI systems, MRI-guided biopsies were also made  possible.

Ultrasound-guided biopsies are  by far the most commonly used procedure. Why? Because they  can be often performed as an office-based procedure. Here are some interesting links to YouTube videos describing such procedures:

  • Prostate

Prostate Ultrasound and Prostate Biopsy by Dr. Neil Baum

Transrectal ultrasound (Trus) Biopsy of the prostate

  • Breast

Ultrasound-Guided Breast Biopsy

Breast Tissue Biopsy

The main advantages: they are easily accessible, low cost and quick. The disadvantages of these procedures are  that they are very much operator dependent, rather than standardized, and there are no quality assurance guidelines attached. Efforts to standardize ultrasound-based biopsies and increase their efficiency are evident by recent introductions of ultrasound systems into the market ,  which support real-time guided biopsies and ultrasound applications that perform real-time biopsy tracking. But these systems are still far from being widely available. I will touch on this issue in my upcoming posts as I am part of these efforts.

CT and Mammography guided biopsies require more sophisticated equipment and well-trained operators. As an example:

Breast Biopsy – What To Expect

The main advantage: if you return to the same operator, the process is likely to be reproducible. The disadvantages are identical to that of ultrasound-based biopsies. It is worthwhile to note that, recently, radiologists who perform biopsies are required to go through a certification process. Still, such certification demands vary between the various radiology societies.

MRI-guided biopsies are an even more sophisticate and complex procedure:

  • Prostate:

DynaTRIM Video

DynaTRIM Intervention

An interesting quote from Dr. Hashim U. Ahmed, M.D., MRCS, Division of Urology  Department of Surgery, University College of London (https://mail.google.com/mail/u/1/?shva=1#label/Work%2FLinks%2FAuntMinnie/139d9c5bc6bda842): “Advocating the widespread use of MRI before biopsy in a population of men with risk parameters for harboring prostate cancer has a number of advantages, which might ultimately benefit the care these men undergo. Increasing the detection of prostate cancer that requires treatment while avoiding biopsy – and hence unnecessary treatment – in those with insignificant or no cancer are compelling arguments for this approach.”

  • Breast

MRI Breast Biopsy – Diagnostic and Biopsy Services for Breast Evaluation

I recommend reading the following article regarding the use of Open MRI to guide freehand biopsies of breast lesions. Especially interesting is the discussion where the authors give a good description of the difficulties in breast biopsies they are trying to overcome in order to achieve good lesion sampling.

MR-guided Freehand Biopsy of Breast Lesions in a 1.0-T Open MR Imager with a Near-Real-time Interactive Platform: Preliminary Experience Frank Fischbach, MD, et. al

http://radiology.rsna.org/content/early/2012/08/14/radiol.12110981.full?sid=bd45ceb4-9c8d-4ffc-b80b-0345ee679b4e

The question remains: which biopsy procedure is the best? And does this question have one coherent answer, i.e. one that will satisfy the patients, the doctors and the health-care insurers?  Will the answer to this question remain the subject of endless uncoordinated clinical studies?

If anyone who reads this post knows on methodological scientific or regulatory initiatives aimed at answering this question on a level of global guide lines  I would appreciate his comment.

Written by: Dror Nir, PhD.

 

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Prostate Cancers Plunged After USPSTF Guidance, Will It Happen Again?

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, FDA Regulatory Affairs, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, tagged , , , , , , on July 31, 2012| 5 Comments »

Prostate Cancers Plunged After USPSTF Guidance, Will It Happen Again?

Reporter: Aviva Lev-Ari, PhD, RN

Article 8.3.Prostate Cancers Plunged After USPSTF Guidance Will It Happen Again

Declines in Prostate Cancer Incidence After Changes in Screening Recommendations

David H. Howard, PhD

Arch Intern Med. 2012;():1-2. doi:10.1001/archinternmed.2012.2768
 

On August 5, 2008, the US Preventive Services Task Force (USPSTF) recommended against screening men 75 years or older for prostate cancer.1 For men younger than 75 years, the USPSTF maintained its previous recommendation: “ . . . the evidence is insufficient to recommend for or against routine screening for prostate cancer. . . ”2 (p915) (although this recommendation was changed to “do not screen” younger men in the 2011 guidelines). This study evaluates trends in prostate cancer incidence following the release of the 2008 USPSTF recommendation. If the revised recommendation led to a decline in prostate cancer screening rates, there should be a corresponding decline in the incidence of early-stage tumors among men 75 and older relative to trends in the incidence of late-stage tumors and early-stage tumors in younger men.

Methods

I measured trends in prostate cancer incidence rates by age group using the Surveillance, Epidemiology and End Results (SEER) 18 registry data, covering 28% of the US population. The SEER registries collect information on all newly diagnosed cancer cases in their respective catchment areas.

Prostate tumors were identified using International Classification of Diseases for Oncology version 3 code 619. I classified cases by stage at diagnosis using the derived American Joint Committee on Cancer summary stage variable: early (T1 or T2), late (T3 or T4), or unknown. I grouped patients into 3 age categories (30-64 years, 65-74 years, and 75 years and older). I calculated incidence rates per 100 000 persons, standardized within age categories by age (in 5-year age groups), race (white, black, American Indian, or other), and ethnicity (Hispanic or not Hispanic) to the 2009 population. I used an unpaired t test for proportions to assess the significance of differences in rates between years. The data were analyzed in Stata version 11 (StataCorp) statistical software.

 Results

The data included 254 184 prostate cancer cases. There were 198 417 early-stage cases, 34 695 late-stage cases, and 21 072 cases of unknown stage. There were 109 053 cases (all stages) among men aged 30 to 64 years, 91 868 cases among men aged 65 to 74 years, and 53 263 cases among men 75 years and older.

The Figure displays the age and race/ethnicity-adjusted incidence rates of early-stage tumors among men aged 65 to 74 years (the upper line) and 75 years and older (the lower line). The trend lines generally mirror each other, but there is a sudden decrease in the incidence of early-stage tumors among men 75 and older after the release of the revised USPSTF recommendation.

Figure. Trends in the incidence of early-stage prostate tumors by age group. Rates are standardized by 5-year age groups and race/ethnicity to the 2009 population. Source: analysis of Surveillance, Epidemiology and End Results (SEER) 18 registry data. USPSTF indicates US Preventive Services Task Force.

Image not available.

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Between 2007 and 2009, the adjusted incidence rate for early-stage tumors among men 75 years and older decreased from 443 to 330 per 100 000 (−25.4%; P < .001). The absolute number of cases declined from 8137 to 6162. The incidence of late-stage tumors decreased from 83 to 71 (−14.3%; P < .001), and the incidence of tumors with unknown stage decreased from 124 to 103 (−16.8%; P < .001). The incidence of early-stage tumors among men aged 65 to 74 years decreased from 697 to 591 (−15.2%; P < .001). The incidence of early-stage tumors among men aged 30 to 64 years decreased from 105 to 93 (−11%; P < .001). Incidence trends for all age and stage groups are given in the eTable.

July 25, 2012 — Nick Mulcahy reports in

http://www.medscape.com/viewarticle/768073?src=nldne

In the past, clinicians and the public have heeded the advice of the United States Preventative Services Task Force (USPSTF) about prostate cancer screening, suggests researchpublished online July 23 in the Archives of Internal Medicine.

After the group’s 2008 guidance, which recommended against screening men older than 75 years, the incidence of early-stage disease in older men plunged 25% in the United States.

“There was an immediate decline in the incidence of early-stage prostate cancer tumors among men 75 years and older after the USPSTF recommended against screening this group,” writes author David Howard, PhD, from the Department of Health Policy and Management at Emory University in Atlanta, Georgia.

The incidence of early-stage disease is an indicator of the amount of prostate-specific antigen (PSA) testing in a population, he explained.

Dr. Howard found that from 2007 to 2009, the adjusted incidence rate for early-stage tumors in men 75 years and older decreased from 443 to 330 per 100,000 (−25.4%; P < .001). The absolute number of cases declined from 8137 to 6162.

Dr. Howard used data from the Surveillance, Epidemiology, and End Results (SEER) 18 registry, which collects information on newly diagnosed cancer cases in catchment areas.

He challenges recent results that indicated that there was no change in PSA screening rates from 2005 to 2010 (JAMA. 2012;307:1692-1694). The data source for that study was the National Health Interview Surveys, in which American residents self-report health behaviors and diseases. “Self-reported PSA testing measures have poor sensitivity and specificity,” scolds Dr. Howard.

An immediate question arises from Dr. Howard’s analysis: Will it happen again because of the 2012 USPSTF recommendation against routine testing for all healthy men?

In an unrelated essay (J Clin Oncol. 2012;30:2581-2584), a group of experts assert that the answer is no.

The USPSTF’s “blanket rejection” of the PSA test is “unlikely to influence practice,” according to Sigrid Carlsson, MD, PhD, from the Memorial-Sloan Kettering Cancer Center in New York City and Göteborg University in Sweden, and colleagues. Dr. Carlsson and her fellow experts wrote an essay criticizing the new USPSTF guideline for a number of “very important errors,” as reported by Medscape Medical News.

“PSA testing is not likely to go away,” wrote Dr. Carlsson and coauthors.

Dr. Howard voiced similar thoughts in an email to Medscape Medical News.

“Physicians are probably more willing to discontinue screening older patients. There might be more resistance to discontinuing screening among younger, healthier men,” he said.

But Dr. Howard also said: “I think it will have an impact. There is growing publicity about the problem of ‘overdiagnosis’, which might make physicians and some patients more receptive to the USPSTF recommendation.”

The recently published PIVOT study might also contribute to the way the new guidance is received, noted Dr. Howard. This major randomized controlled trial found that prostatectomy did not improve survival significantly, compared with observation, in men with localized disease. “This research also casts doubt on the benefits of early detection, which may amplify the impact of the USPSTF recommendation,” said Dr. Howard about PIVOT.

Nonetheless, “many men will continue to receive regular PSA tests,” he added.

More Details

In addition to finding that the rate of early-stage prostate cancers dropped among older men after the 2008 recommendation, Dr. Howard found that other indicators of PSA testing also dropped.

The incidence of late-stage tumors decreased by 14.3% (P < .001), and the incidence of tumors of unknown stage decreased by 16.8% (P < .001). The incidence of early-stage tumors in men 65 to 74 years decreased by 15.2% (P < .001); in men 30 to 64 years, the incidence decreased by 11% (P < .001).

Overall, Dr. Howard found that 254,184 prostate cancer cases were newly diagnosed during the study period. There were 198,417 early-stage cases, 34,695 late-stage cases, and 21,072 cases of unknown stage. There were 109,053 cases (all stages) in men 30 to 64 years of age, 91,868 cases in men 65 to 74 years, and 53,263 cases in men 75 years and older.

As noted above, the incidence rate trends turned sharply downward in 2009, after the 2008 USPSTF report.

REFERENCES

1
US Preventive Services Task Force.  Screening for prostate cancer: US Preventive Services Task Force recommendation statement.  Ann Intern Med. 2008;149(3):185-191

2
US Preventive Services Task Force.  Screening for prostate cancer: recommendation and rationale.  Ann Intern Med. 2002;137(11):915-916

3
Prasad SM, Drazer MW, Huo D, Hu JC, Eggener SE. 2008 US Preventive Services Task Force recommendations and prostate cancer screening rates.  JAMA. 2012;307(16):1692-1694

4
Hall HI, Van Den Eeden SK, Tolsma DD,  et al.  Testing for prostate and colorectal cancer: comparison of self-report and medical record audit.  Prev Med. 2004;39(1):27-35

5
Chan EC, Vernon SW, Ahn C, Greisinger A. Do men know that they have had a prostate-specific antigen test? accuracy of self-reports of testing at 2 sites.  Am J Public Health. 2004;94(8):1336-1338

6
Guerra CE, Jacobs SE, Holmes JH, Shea JA. Are physicians discussing prostate cancer screening with their patients and why or why not? a pilot study.  J Gen Intern Med. 2007;22(7):901-907

7
Linder SK, Hawley ST, Cooper CP, Scholl LE, Jibaja-Weiss M, Volk RJ. Primary care physicians’ reported use of pre-screening discussions for prostate cancer screening: a cross-sectional survey.  BMC Fam Pract. 2009;1019

 

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New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, tagged , , , , , , , on May 27, 2012| 3 Comments »

New Prostate Cancer Screening Guidelines Face a Tough Sell, Study Suggests

Reporter: Prabodh Kandala, PhD

Article 8.4.New Prostate Cancer Screening Guidelines Face a Tough Sell Study Suggests

Recent recommendations from the U.S. Preventive Services Task Force (USPSTF) advising elimination of routine prostate-specific antigen (PSA) screening for prostate cancer in healthy men are likely to encounter serious pushback from primary care physicians, according to results of a survey by Johns Hopkins investigators.

In a survey of 125 primary care doctors, the researchers found that while doctors agreed with older recommendations to curtail routine screening in men over age 75 and among those not expected to live 10 or more years, a large number said they faced significant barriers to stopping PSA testing in men who had been receiving it regularly. The most frequently cited reason by 74.4 percent of physicians was, “My patients expect me to continue getting yearly PSA tests,” followed by 66 percent of them who said, “It takes more time to explain why I’m not screening than to just continue screening.” More than half of those surveyed in the new study believed that, “By not ordering a PSA, it puts me at risk for malpractice.”

The survey was conducted in November 2011, right after draft recommendations were made to end routine screening of all men, but before last week, when the draft recommendations were officially approved.

“It can be very difficult for doctors to break down the belief that all cancer screening tests are invariably good for all people all the time,” says Craig E. Pollack, M.D., M.H.S., an assistant professor in the Division of General Internal Medicine at the Johns Hopkins University School of Medicine, and leader of the study published online in the journal Cancer. “Everyone agrees that PSA screening isn’t as good as we want it to be. If we had a test that was a slam dunk, it would be different. But now we know that for many men, the benefits may be small and the harms significant.”

Each year, more than 33,000 American men die of prostate cancer, and 20 million get the PSA test to detect the disease early.

According to the USPSTF, evidence suggests the potential harms caused by PSA screening of healthy men as a means of identifying prostate cancer outweigh its potential to save lives and that routine annual screening should be eliminated in the healthy. Elevated PSA readings are not necessarily evidence of prostate cancer, and can lead to unnecessary prostate biopsy. In addition, even when biopsies reveal signs of prostate cancer cells, evidence shows that a large proportion will never cause harm, even if left untreated. The disease in older men often progresses slowly so that those who have it frequently die of other causes.

Treatments for prostate cancer can include the removal of the prostate, radiation or other therapies, each of which has the potential to cause serious problems like erectile dysfunction, complete impotence, urinary incontinence or bowel damage. And men who choose to “watch and wait” after elevated PSA readings must live with the anxiety of knowing they have an untreated cancer that could start to progress.

In the new study, Pollack and his colleagues found that while most physicians said they took age and life expectancy into account when deciding to order PSA screening, many also said they had a hard time estimating life expectancy in their patients and could use a better tool. H. Ballentine Carter, M.D., a professor of urology at Johns Hopkins and the senior investigator on the study, is planning to investigate the potential of individualized prostate cancer screening recommendations. Specifically, he and colleagues plan to create a decision-making tool that incorporates age, life expectancy, family history and prior PSA results in order to help doctors and their patients make better choices for prostate cancer screening.

In another report derived from results of Pollack’s and Carter’s survey, published in April in the Archives of Internal Medicine, the researchers say nearly half of the providers agreed with the new USPSTF recommendations to eliminate routine screening for healthy men. Still, less than two percent said they would no longer order routine PSA screening in response to the draft recommendations; 21.9 percent said they would be much less likely to do so; 38.6 percent said they would be somewhat less likely to do so; and 37.7 percent said they would not change their screening practices.

“Men often expect PSA screening to be part of their annual physical,” Pollack says. “To change their minds, we need to address their perceptions about screening, allow time for screening discussions and reduce concerns regarding malpractice litigation.”

Ref: http://www.sciencedaily.com/releases/2012/05/120526191324.htm

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