Can a Pill Plus Infrared Light Replace Mammograms? Interview with:

Greg Thurber, PhD Assistant Professor Department of Chemical Engineering Assistant Professor Department of Biomedical Engineering University of Michigan 

Dr. Thurber

Greg Thurber, PhD
Assistant Professor
Department of Chemical Engineering
Assistant Professor
Department of Biomedical Engineering
University of Michigan What is the background for this study?

Response: Most current disease screening strategies rely on either blood tests, where the physician can obtain information on specific disease molecules but has no idea where they originated in the body, or anatomical imaging, where the physician can see changes in the structure of tissues but doesn’t have any molecular information. We wanted to develop a method that could provide both molecular information and an image of where these molecules were located. We know from decades of research in cancer that this is a molecular disease, so providing molecular information to the physician will help improve detection and diagnosis. Breast cancer screening provides an excellent opportunity to apply this approach to improve detection. Currently, estimates indicate that we are overspending $4 billion per year on the overdiagnosis and overtreatment of breast cancer because we cannot accurately determine which patients need treatment and which can be safely monitored with no intervention. Despite this problem with overdiagnosis, however, screening saves lives…we simply need a better way.

Molecular imaging has the capability of providing both molecular information and the location within the body. However, most of these techniques are expensive and use ionizing radiation, meaning there is a small risk of actually causing cancer. This is not acceptable for screening large numbers of otherwise healthy patients. To avoid this risk and provide a safe, inexpensive, and relatively easy method for patients to undergo screening, we decided to develop near-infrared fluorescent imaging agents that can be taken as a pill. The goal is for the patient to simply take a pill a day or two before their visit, and then the physician shines near-infrared light on the breast tissue to detect tumors where they ‘light up’ by giving off a different color of light.

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Investigational Imaging Test Can Help Determine Success or Failure of Bone Marrow Transplant Interview with:

Kirsten Williams, M.D. Blood and marrow transplant specialist Children’s National Health System

Dr. Williams

Kirsten Williams, M.D.
Blood and marrow transplant specialist
Children’s National Health System What is the background for this study? What are the main findings? 

Response: This study addressed a life-threatening complication of bone marrow transplantation called bone marrow failure. Bone marrow transplantation has provided a cure for patients with aggressive leukemias or acquired or genetic marrow dysfunction. The process of bone marrow transplantation involves giving chemotherapy and/or radiation, which removes the diseased blood cells from the bone marrow. After this, new bone marrow stem cells are infused from a healthy individual. They travel to the bone marrow and start the slow process of remaking the blood system. Because these new cells start from infancy, it takes upwards of four to five weeks for new mature healthy cells to emerge into the blood, where they can be identified. Historically, there has been no timely way to determine if the new cells have successfully repopulated unless they can be seen in the blood compartment. This condition of bone marrow failure is life-threatening, because patients don’t have white blood cells to protect them from infection. Once bone marrow failure is diagnosed, a second new set of stem cells are infused, often after more chemotherapy is given. However, for many individuals this re-transplantation is too late, because severe infections can be fatal while waiting cells to recover.

We were the first group to use a new imaging test to understand how the newly infused bone marrow cells develop inside the patient. We have recently published a way to detect the new bone marrow cell growth as early as five days after the cells are given. We used an investigational nuclear medicine test to reveal this early cell growth, which could be detected weeks before the cells appear in the blood. This radiology test is safe, does not cause any problems and is not invasive. It is called FLT (18F-fluorothymidine) and the contrast is taken up by dividing hematopoietic stem cells. The patients could even see the growth of their new cells inside the bone marrow (which they very much enjoyed while waiting to see recovery of the cells in their blood). We could use the brightness of the image (called SUV) to determine approximately how many weeks remained before the cells were visible in the blood.

Finally, we actually could see where the new cells went after they were infused, tracking their settling in various organs and bones. Through this, we could see that cells did not travel directly to all of the bones right away as was previously thought, but rather first went to the liver and spleen, then to the mid-spine (thorax), then to the remainder of the spine and breastplate, and finally to the arms and legs. This pattern of bone marrow development is seen in healthy developing fetuses. In this case, it occurs in a similar pattern in adults undergoing bone marrow transplant.

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Diagnostic Accuracy of FFR-CT Varies Across Spectrum of Coronary Artery Disease Interview with:
Dr Christopher Michael Cook MBBS Bsc(Hons) MRCP

MRC Clinical Research Fellow
NHLI, Cardiovascular Medicine, Imperial College London What is the background for this study?

Response: FFR-CT is a novel non-invasive technique for estimating the functional significance of a coronary stenosis from CT coronary angiography images. A number of meta-analyses already exist for determining the diagnostic accuracy of FFR-CT (compared to invasive FFR as the reference standard). However, although knowing the overall diagnostic accuracy of FFR-CT is reassuring, in clinical practice a clinician knows not only whether the FFR-CT is positive or negative, but also its actual value. The purpose of this study was to provide clinicians a means of interpreting the diagnostic accuracy of any individual FFR-CT result that may be received in clinical practice. What are the main findings?

Response: The main finding of this study is that the diagnostic accuracy of FFR-CT varies markedly across the spectrum of disease. For vessels with FFR-CT above 0.90, 98% met the invasive FFR guideline criterion for deferral. At the other end of the spectrum, for vessels with FFR-CT below 0.60, 86% met the invasive FFR guideline criterion for stenting. However, in between, FFR-CT gives less certainty as to whether the invasive FFR will meet the stenting criterion or not. What should readers take away from your report?

Response: Readers can combine the findings of our study with patient specific factors in order to judge when the cost and risk of an invasive angiogram may safely be avoided. Because we now have a more complete picture of what different levels of FFR-CT mean in terms of invasive FFR, it is apparent that a single cut-off value for FFR-CT in deciding on invasive coronary angiography need not always apply. For example, in the asymptomatic patient, further investigations may not be desirable even if an FFR-CT still left a substantial possibility of a positive invasive FFR. Conversely, in the symptomatic patient, the patient and clinician would likely pursue invasive angiography unless the possibility of a positive FFR is very remote. What recommendations do you have for future research as a result of this study?

Response: This study adopted novel methodology to ascertain the probability that both FFR-CT and invasive FFR agreed on the functional classification of a stenosis, for any given individual FFR-CT value. This type of analysis could be used to determine if further iterative versions of the FFR-CT software translate into improved diagnostic performance, particularly in more intermediate disease severities. Is there anything else you would like to add?

Response: Thank you for your contribution to the community.


Cook CM, Petraco R, Shun-Shin MJ, Ahmad Y, Nijjer S, Al-Lamee R, Kikuta Y, Shiono Y, Mayet J, Francis DP, Sen S, Davies JE. Diagnostic Accuracy of Computed Tomography–Derived Fractional Flow Reserve A Systematic Review . JAMA Cardiol. Published online May 24, 2017. doi:10.1001/jamacardio.2017.1314

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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iFR Can Assess Need For Coronary Revascularization Without Adenosine Interview with:

Dr. Justin Davies PhD Senior Reserch Fellow and Hononary Consultant Cardiologist National Heart and Lung Institute, Imperial College Londo

Dr. Davies

Dr. Justin Davies PhD
Senior Reserch Fellow and Hononary Consultant Cardiologist
National Heart and Lung Institute,
Imperial College London What is the background for this study?

Response: We know from the FAME study that compared to angiography alone, FFR guided revascularization improves long-term clinical outcomes for our patients. Despite this, adoption of FFR into everyday clinical practice remains stubbornly low. One major factor for this is the need for adenosine (or other potent vasodilator medications) in order to perform an FFR measurement. Adenosine is expensive, unpleasant for the patient, time consuming and even potentially harmful.

iFR is a newer coronary physiology index that does not require adenosine for its measurement. In the prospective, multi center, blinded DEFINE FLAIR study, 2492 patients were randomly assigned to either FFR guided revascularisation or iFR guided revascularization and followed up for a period of 1 year.
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Instantaneous Wave-free Ratio vs Fractional Flow Reserve to Guide PCI Interview with:

Dr. Matthias Götberg MD PhD Department of Cardiology, Clinical Sciences Lund University, Skåne University Hospital Lund, Sweden

Dr. Matthias Götberg

Dr. Matthias Götberg MD PhD
Department of Cardiology, Clinical Sciences
Lund University, Skåne University Hospital
Lund, Sweden What is the background for this study?

Response: Cardiologists encounter patients with narrowing of the coronary arteries on a daily basis. They typically use visual estimation of the severity of narrowing when performing coronary angiography, but it is difficult to accurately assess, based on a visual estimation alone, whether a stent is needed to widen the artery and allow the blood to more freely.

FFR (Fractional Flow Reserve) is more precise tool and results in better outcomes than using angiography alone to assess narrowing of the coronary arteries. With FFR, the doctor threads a thin wire through the coronary artery and measures the loss of blood pressure across the narrowed area. To acquire an accurate measurement, the patient must be given adenosine, which is a drug that dilates the blood vessels during the procedure. This drug causes discomfort; patients describe having difficulty breathing or feeling as if someone is sitting on their chest. The drug also adds to the cost of the procedure and can have other rare but serious side effects.

iFR (Instantaneous Wave-Free Ratio) is also based on coronary blood pressure measurements using a thin wire, but unlike FFR, it uses a mathematical algorithm to measure the pressure in the coronary artery only when the heart is relaxed and the coronary blood flow is high. As a result, a vasodilator drug is not needed.

iFR has been validated in smaller trials and have been found to be equally good as FFR to detect ischemia, but larger randomized outcome trials are lacking.

iFR-Swedeheart is a Scandinavian Registry-based Randomized Clinical Trial (RRCT) in which 2000 patients were randomized between iFR and FFR as strategies for performing assessment of narrowed coronary vessels. The primary composite endpoint at 12 months was all-cause death, non-fatal myocardial infarction, and unplanned revascularization.

RRCT is a new trial design originating from Scandinavia using existing web-based national quality registries for online data entry, randomization and tracking of events. This allows for a very high inclusion rate and low costs to run clinical trials while ensuring robust data quality.  Continue reading

SPECT MPI to Predict Heart Attacks: Stress Agents Regadenoson vs Adenosine

Dr. Afshin Farzaneh-Far, M.D. University of Illinois at Interview with:
Dr. Afshin Farzaneh-Far, M.D.

University of Illinois at Chicago What are the main findings of the study?

Answer: Traditionally SPECT MPI has been performed with adenosine which has a
significant body of published prognostic data.

Regadenoson is a selective A2A receptor agonist and is now the stress
agent most widely used in the United States. Unlike adenosine, regadenoson
is given as a bolus rather than as an infusion, simplifying the testing
protocol and is better-tolerated.

However, despite increasing use of regadenoson, there is very limited data
on risk prediction using this agent.

This study showed that the ability of SPECT MPI to predict heart attacks
and death is the same for the new stress agent Regadenoson as it is for
the old agent Adenosine.

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