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Posts Tagged ‘breast cancer screening’


Author and Curator: Dror Nir, PhD

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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Author: Dror Nir, PhD

 

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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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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