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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Machines Can Be Taught Natural Language Processing To Read Radiology Reports Interview with:

Eric Karl Oermann, MD Instructor Department of Neurosurgery Mount Sinai Health System New York, New York 10029 

Dr. Oermann

Eric Karl Oermann, MD
Department of Neurosurgery
Mount Sinai Health System
New York, New York 10029 What is the background for this study? What are the main findings? 

Response: Supervised machine learning requires data consisting of features and labels. In order to do machine learning with medical imaging, we need ways of obtaining labels, and one promising means of doing so is by utilizing natural language processing (NLP) to extract labels from physician’s descriptions of the images (typically contained in reports).

Our main finding was that (1) the language employed in Radiology reports is simpler than normal day-to-day language, and (2) that we can build NLP models that obtain excellent results at extracting labels when compared to manually extracted labels from physicians.  Continue reading

PSMA PET/CT Can Map Prostate Cancer Recurrences With Very Low PSA Levels Interview with:
Jeremie Calais PhD Ahmanson Translational Imaging Division UCLA Nuclear Medicine Department Los Angeles, CA 90095Jeremie Calais MD

Ahmanson Translational Imaging Division
UCLA Nuclear Medicine Department
Los Angeles, CA 90095 What is the background for this study? What are the main findings?

Response: The only curative treatment for recurrent prostate cancer after radical prostatectomy is salvage radiotherapy. Unfortunately, current standard imaging modalities are too insensitive to visualize the location of the recurrence until it is too late. As a result, salvage radiotherapy is directed to areas only suspected to harbor the recurrence based upon a “best guess” approach according to standard guidelines that define radiotherapy treatment volumes.

PSMA PET/CT is a new imaging technique with sensitivity sufficient to detect and localize the recurrent prostate cancer early enough to potentially guide salvage radiotherapy.

The first sign of prostate cancer recurrence is a rising PSA. For salvage radiotherapy to be successful, it should be initiated before the PSA rises above 1 ng/mL, and ideally, closer to 0.2 ng/mL or lower. PSMA PET/CT localizes sites of prostate cancer recurrence in up to 70% of patients with low PSA, below < 1.0.

In the US it is not yet FDA approved and currently only used for research purposes. In our current study we included 270 patients with early recurrence of prostate cancer after surgery from Germany and UCLA,  we found that 20 % of the patients had at least one lesion detected by  PSMA PET/CT which was NOT covered by the standard radiation fields. Obviously, salvage radiotherapy is only curative if recurrent disease is completely encompassed by the radiotherapy fields and would have failed in these patients.

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Multiple Sclerosis: Functional Changes After Inflammation May Partly Explain Clinico-Radiological Paradox Interview with:
Netta Levin MD PhD
fMRI lab
Neurology Department
Hadassah Hebrew University Medical Center
Jerusalem What is the background for this study?

Response: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, manifesting with episodes of local inflammatory processes, called relapses. The most useful surrogate laboratory test for MS is magnetic resonance imaging (MRI), in which dissemination of demyelinating lesions in space and time are the hallmark of the disease. However, there is a discrepancy between the lesion load – the number, size, and location of the lesions – and the clinical state of the patients, reflected in their disability. This discrepancy is known as the “clinico-radiological paradox” and suggests that something other than the well-known mechanisms of demyelination, remyelination, and axonal loss may tip the scale of recovery from an acute episode. Global effects of the local damage and compensatory mechanisms were suggested as an explanation to this paradox.

In this study, we compared the visual system of patients with clinically isolated syndrome optic neuritis (ON) to patients with clinically isolated episodes in other functional systems, exploring changes, both anatomical and functional, caused to the system following the demyelinating episode. Optic neuritis was deemed a good in vivo model for studying the pathophysiology of tissue damage and repair in MS due to its characteristic clinical manifestation and to the visual pathways’ amenability to investigation using various techniques. To assess anatomical wiring ,i.e the white matter fibers themselves , we used diffusion tensor imaging (DTI). To assess functional networking as reflected by signal synchronization between distinct brain regions, we used resting state fMRI.

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Radiologic Findings Can Be Key In Identifying Intimate Partner Violence Interview with:
“IMGP6403_qtu-no-violence” by Rae Allen is licensed under CC BY 2.0
Elizabeth George, MD
PGY-4 Radiology Resident
Brigham and Women’s Hospital
Dr. Bharti Khurana MD
Clinical Fellow, Harvard Medical School and
Assistant Director, Emergency Radiology
Director, Emergency Musculoskeletal Radiology
Program Director, Emergency Radiology Fellowship
Assistant Professor, Harvard Medical School What is the background for this study? What are the main findings?

Response: According to the CDC, 1 in 3 women in the United States are victims of abuse by their intimate partner. Despite the US Preventive Services Task Force recommendations, intimate partner violence (IPV) screening is still not widely implemented and IPV remains very prevalent and often under-recognized.

The goals of this study are to increase the awareness among physicians about this public health problem and to elucidate the potential role of imaging in the identification of these patients. In fact, there is a striking disparity in the literature on the role of imaging in identifying non-accidental trauma in children compared to intimate partner violence.

The common patterns of injury we identified in this population were soft tissue injuries (swelling, hematoma or contusion) followed by extremity fractures, which often involve the distal upper extremities, suggesting injury from defensive attempts. Other common injuries were facial fractures, which represent an easily accessible site for inflicting trauma, and pregnancy failure. Since radiologists have access to both current and prior radiological studies of these patients, they could play a critical role by putting the pieces together in identifying victims of IPV.

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FDG-PET Scans of Lung Nodules Should Be Interpreted With Caution Interview with:

PET Scan Vanderbilt Health

PET Scan Vanderbilt Health

Amelia W. Maiga, MD MPH
Vanderbilt General Surgery Resident
VA Quality Scholar, TVHS What is the background for this study? What are the main findings?

Response: Positron emission tomography (PET) combined with fludeoxyglucose F18 (FDG) is currently recommended for the noninvasive diagnosis of lung nodules suspicious for lung cancer. Our investigation adds to growing evidence that FDG-PET scans should be interpreted with caution in the diagnosis of lung cancer. Misdiagnosis of lung lesions driven by FDG-PET avidity can lead to unnecessary tests and surgeries for patients, along with potentially additional complications and mortality.

To estimate FDG-PET diagnostic accuracy, we conducted a multi-center retrospective cohort study. The seven cohorts originating from Tennessee, Arizona, Massachusetts and Virginia together comprised 1188 nodules, 81 percent of which were malignant. Smaller nodules were missed by FDG-PET imaging. Surprisingly, negative PET scans were also not reliable indicators of the absence of disease, especially in patients with smaller nodules or who are known to have a high probability of lung cancer prior to the FDG-PET test.

Our study supports a previous meta-analyses that found FDG-PET to be less reliable in regions of the country where fungal lung diseases are endemic. The most common fungal lung diseases in the United States are histoplasmosis, coccidioidomycosis and blastomycosis. All three fungi reside in soils. Histoplasmosis and blastomycosis are common across much of the Mississippi, Ohio and Missouri river valleys and coccidioidomycosis is prevalent in the southwestern U.S. These infections generate inflamed nodules in the lungs (granulomas), which can be mistaken for cancerous lesions by imaging.

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Granzyme B Probe Plus PET Scanning Helps Determine Response To Immunotherapy Interview with:

Ben Larimer, PhD research fellow in lab of Umar Mahmood, MD, PhD Massachusetts General Hospital Professor, Radiology, Harvard Medical School

Dr. Ben Larimer

Ben Larimer, PhD research fellow in lab of
Umar Mahmood, MD, PhD

Massachusetts General Hospital
Professor, Radiology, Harvard Medical School What is the background for this study? What are the main findings?

Although immunotherapies such as checkpoint inhibitors have revolutionized cancer treatment, unfortunately they only work in a minority of patients. This means that most people who are put on a checkpoint inhibitor will not benefit but still have the increased risk of side effects. They also lose time they could have spent on other therapies. The ability to differentiate early in the course of treatment patients who are likely to benefit from immunotherapy from those who will not greatly improves individual patient care and helps accelerate the development of new therapies.

The main purpose of our study was to find a way to separate immunotherapy responders from non-responders at the earliest time point possible, and develop an imaging probe that would allow us to distinguish this non-invasively.

Granzyme B is a protein that immune cells use to actually kill their target. They keep it locked up in special compartments until they get the right signal to kill, after which they release it along with another protein called perforin that allows it to go inside of tumor cells and kill them. We designed a probe that only binds to granzyme B after it is released from immune cells, so that we could directly measure immune cell killing. We then attached it to a radioactive atom that quickly decays, so we could use PET scanning to noninvasively image the entire body to see where immune cells were actively releasing tumor-killing granzyme B.

We took genetically identical mice and gave them identical cancer and then treated every mouse with checkpoint inhibitors, which we knew would result in roughly half of the mice responding, but we wouldn’t know which ones until their tumors began to shrink. A little over a week after giving therapy to the mice, and before any of the tumors started to shrink, we injected our imaging probe and performed PET scans. When we looked at the mice by PET imaging, they fell into two groups. One group had high PET uptake, meaning high levels of granzyme B in the tumors, the other group had low levels of PET signal in the tumors. When we then followed out the two groups, all of the mice with high granzyme B PET uptake ended up responding to the therapy and their tumors subsequently disappeared, whereas those with low uptake had their tumors continue to grow.

We were very excited about this and so we expanded our collaboration with co-authors Keith Flaherty and Genevieve Boland to get patient samples from patients who were on checkpoint inhibitor therapy to see if the same pattern held true in humans. When we looked at the human melanoma tumor samples we saw the same pattern, high secreted granzyme levels in responders and much lower levels in non-responders.

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Medicare Has Cut Radiology Payments To Physicians by 33% Over Ten Years Interview with:
David C. Levin, MD

Department of Radiology
Thomas Jefferson University Hospital
Philadelphia, PA 19107. What is the background for this study? What are the main findings?

Response: Radiology had been previously identified as the most rapidly growing of all physician services in the Medicare program during the early years of the 2000-2009 decade. But there have been deep cuts in imaging reimbursement since then. We wanted to determine how these cuts have affected total Medicare payments for imaging.

Our main findings were that since 2006, payments to physicians for imaging under the Medicare Physician Fee schedule have dropped by $4 billion per year, or about 33%.

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Radiation Exposure in the Pediatric Patient: What Every Orthopaedist Should Know Interview with:
Ayesha Rahman, MD

Chief Orthopaedic Surgery Resident
NYU Langone Medical Center. What is the background for this study? What are the main findings?

Response: Children are more vulnerable and susceptible to lifetime adverse events from radiation exposure, caused by imaging . We reviewed literature and found certain pediatric orthopaedic patients are at greater risk for radiation exposure, namely those who have surgery for hip dysplasia, scoliosis, and leg length discrepancy, as they are among those most likely to undergo CT imaging. After reviewing all types of imaging studies performed in orthopedics and how much radiation is involved in each test, we developed several recommendations that pediatric orthopaedic surgeons should follow.

Among those recommendations are: utilize low-dose CT protocols or technology that uses less imaging (like EOS), limit CT scans of the spine and pelvis, know that female patients are more susceptible to adverse risk and plan accordingly, and follow the the “as low as reasonably achievable,”principle to limit exposure to parts of the body that are necessary for diagnosis.

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Prostate Artery Embolization Is Less Invasive Choice For BPH Treatment Interview with:

Dr. João Martins Pisco, MD PhD Hospital St. Louis, International Prostate Medical Center Lisbon, Portugal

Dr. João Martins Pisco

Dr. João Martins Pisco, MD PhD
Hospital St. Louis, International Prostate Medical Center
Lisbon, Portugal What is the background for this study? What are the main findings?

Response: Enlarged prostate, also known as benign prostatic hyperplasia (BPH), is one of the most common prostate problems occurring in men older than 50. According to the National Institutes of Health, as many as 14 million men in the U.S. had symptoms suggestive of BPH, which can affect 50 percent of men between 51 and 60 years of age and up to 90 percent of men older than 80. A few years ago, Dr. João Martins Pisco developed the minimally invasive treatment, known as prostate artery embolization, to treat BPH. The study that Dr. Pisco presented at the Society of Interventional Radiology on March 8 is the first of its kind – a study with 1,000 patients with long-term efficacy data.

Between March 2007 and March 2016, Dr. Pisco and his team performed PAE on 1,000 men who averaged 67 years of age. All patients were evaluated in the short term (one, three, and six months), 807 patients were seen through the medium term (every six months between six months and three years), and 406 patients were evaluated long term (every year after three years).

During each evaluation, the men’s symptoms were measured by the International Prostate Symptom Score (IPSS), which tests for the blockage of urine flow, and the International Index of Erectile Function (IIEF), which assesses erectile dysfunction. Researchers also measured the size of the prostate and the amount of urine left in the bladder after urination. They also evaluated the peak urinary flow rate and the prostate-specific antigen (PSA) level, a test used to screen for prostate cancer.  What are the main findings?

Response:  The data from these measures revealed at the short-term mark that the treatment had an 89 percent cumulative success rate—measuring the success across all variables through the given testing period. The 807 men evaluated at the medium-term mark had an 82 percent success rate. And of the 406 patients measured at the long-term mark, 78 percent were considered cumulative successes.

In an additional analysis, researchers found that among 112 patients who also suffered acute urinary retention (AUR) before undergoing PAE, 106 or 94.6 percent had their catheter removed between two days and three months after treatment. At medium-term and long-term follow up, 95 of the 112 (84.8 percent) and 89 of the 112 (78.5 percent) did not experience any recurrence of their AUR.

The team also performed PAE in 210 patients who had limited treatment options due to extreme enlargement of the prostate (larger than 100 cm³). Of these men, 84 percent experienced cumulative success at short-term evaluation and 76.2 percent at medium- and long-term. The normal size of a prostate is 15 cm3 to 30 cm3. What should readers take away from your report?

Response:  Prostate artery embolization gives men with BPH a treatment option that is less invasive than other therapies and allows them to return to their normal lives sooner. Time and time again, Dr. Pisco has seen patients who are relieved to find out about PAE because they are not able to tolerate medications for BPH due to their side effects. These men also don’t want traditional surgery because it involves greater risks, has possible sexual side effects, and has a recovery time that is relatively long compared to PAE, which is generally performed under local anesthesia and on an outpatient basis.

Prostate artery embolization should also be presented to patients who are exploring options to resolve their BPH.

That said, PAE may not be appropriate for all patients, such as those with advanced arterial atherosclerosis that may be due to smoking or diabetes. Patients should speak with an interventional radiologist or other members of their care team to discuss treatment options. What recommendations do you have for future research as a result of this study?

Response: As a next step, Dr. Pisco and his team are now conducting a study comparing the effectiveness of PAE to a sham – or placebo—treatment to address any possible placebo effect that may have occurred during Pisco’s research with these 1,000 patients. Is there anything else you would like to add?

Response: Prostate artery embolization is a safe and effective treatment and these data demonstrate the efficacy of the therapy in the long term. It’s important that patients know about this therapy as they explore how to resolve their BPH. Thank you for your contribution to the community.


Society of Interventional Radiology abstract discussing:

Prostate artery embolization for BPH

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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