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A new MRI technique can measure the levels of water exchange across the blood-brain barrier (BBB), identifying dysfunction that is associated with the development of small vessel disease (SVD).

Cerebral SVD is the most common form of vascular cognitive impairment, and many individuals who have it go on to develop dementia. The BBB is responsible for clearing the brain of toxic substances, and a malfunction is widely considered to be an early marker of SVD.

PET scans and dynamic contrast-enhanced (DCE) MRI can effectively detect damage to the BBB, but these measures also subject patients to radiation and contrast dye. They are also limited because they generally only pick up later-stage BBB dysfunction. Consequently, there is a need for a non-invasive technique that can catch problems earlier, said a team of investigators from the University of Kentucky and the University of Southern California.

Leaky Blood-Brain Barrier Causes Brain Damage Before MRI Catches Lesions

Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association

the team detailed their solution: diffusion-prepared arterial spin labeling (DP-ASL), a non-invasive technique developed by Xingfeng Shao, Ph.D., a research scientist, and Danny Wang, Ph.D., a neurology and radiology professor, both with the USC Mark and Mary Stevens Neuroimaging and Informatics Institute. This MRI method measures the subtle BBB dysfunctions that are associated with a modified water exchange rate across the BBB.

“Our results provide evidence for an in vivo association between water exchange rate across the BBB and cerebral spinal fluid (CSF) amyloid-beta42 concentration,” said the team. “These findings suggest that [water exchange rate across the BBB] computed from a novel DP-ASL sequence may be a potential indicator of BBB-related clearance functions.”

To make this determination, the team conducted DP-ASL sequence MRI scans on 39 healthy older adults without any cognitive impairment between the ages 67 and 86. Participants were scanned with 3T scanners, using a 64-channel head coil, and the team used high-resolution, multi-echo, T1-weighted anatomical image and 3D gradient-and-spin echo diffusion-prepared pCASL sequences. In addition, the patients underwent a lumbar CSF draw.

For their assessment, the team concentrated on levels of amyloid-beta in the CSF – levels are low when the protein is not sufficiently cleared from the brain into the CSF. Based on their evaluation, the team determined that low CSF amyloid-beta levels were associated with a low BBB water exchange rate captured by the DP-ASL method.

In addition, they identified significant associations between CSF amyloid-beta42 concentration and water exchange values in the whole brain (beta=0.51, t=3.4, P=0.002, VIF=1.04), frontal lobe (beta=0.50, t-3.4, P=0.02, VIF=1.04), parietal lobe (beta=0.56, t=3.9, P<0.001, VIF=1.03), and precuneus (beta=0.46, t=3.1, P=0.004, VIF=1.02) after controlling for sex and age. Each measurement, they said was associated with low CSF amyloid-beta42 concentration.

“Our results suggest that DP-ASL may provide a non-invasive index of BBB clearance dysfunction prior to any detectable cognitive impairment,” said Brian Gold, Ph.D., a neuroscience professor at the University of Kentucky Sanders-Brown Center on Aging.

Ultimately, the team said, these results add to the growing body of evidence that BBB dysfunction could represent a link between SVD and a clinical diagnosis for Alzheimer’s, and DP-ASL could be used to non-invasively assess BBB water exchange in SVD clinical trials.

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Articles

Diffusion-prepared arterial spin labeling can measure the water exchange rate across the blood-brain barrier, catching malfunctions at an earlier state.

New MRI Technique Identifies Early-Stage BBB Dysfunction with Small Vessel Disease

 Wall thickening of the ileum is seen on follow-through of GI series on fluoroscopy. Findings are consistent with inflammation of the terminal ileum in Crohn’s disease.

 In the small bowel, in Crohn’s disease, there can be skip lesions and discrete ulcers. The terminal ileum is usually affected first, but remaining segments of the small bowel are also commonly affected. On fluoroscopy, on small bowel follow-through, mucosal ulcers can be seen and widely separated bowel loops of bowel can also be seen due to fatty proliferation (“creeping fat”). There can also be the “string sign” seen, which is narrowing or spasm of small bowel segments. Look for partial bowel obstructions and also pseudodiverticulum formation.

What is causing this appearance on small bowel GI series follow-through?

Image IQ Quiz: What Do You See on This Small Bowel GI Series?

Women who have lower levels of a fibroblast protein that is integral to the development of the cardiovascular system – PDGFRb – have a better response to radiotherapy treatment for early-stage breast cancer.

For ductal carcinoma in situ (DCIS), the current treatment is surgery and subsequent radiotherapy. Long-term outcomes are generally good, but up to 10 percent of women do suffer a recurrent within 10 years. Consequently, unearthing a more personalized way to treat these women is vital, said investigators from Karolinska Institutet and Gothenburg University in Sweden.

“It is well known that the benefits of radiotherapy are individual, so we need to find predictive markers that can be used to avoid unnecessary or ineffective radiotherapy,” said Fredrik Wärnberg, professor in the clinical sciences department at Gothenburg University’s Sahlgrenska Academy.

The team, co-led by Wärnberg, published their findings recently in 

Instead of focusing on markers within the tumor cells, the team pivoted to examine the role cells surrounding the tumor might play in the efficacy of radiotherapy. To do so, researchers analyzed a large tissue collection from a randomized radiotherapy study (SweDCIS), and they found that women who have low PDGFRb levels have better outcomes with radiotherapy for ipsilateral breast events (IBE).

Specifically, women with low PDGFRb experience an absolute risk reduction of recurrence of 21 percent at 10 years. This predictive effect was equally strong for women with in situ and invasive IBE. Unfortunately, women with high PDGFRb levels did not see a significant risk reduction.

These results, the team said, support the possibility of changing approaches to therapy.

“The treatment guidelines of DCIS might need to be changed if these studies confirm our original findings,” said first author Carina Strell, a researcher oncology-pathology department at Karolinska Institutet.

Additional work is underway to investigate whether radiotherapy efficacy can be further improved by blocking PDGFRb.

Women with low levels of PDGFRb, a protein involved in cardiovascular development, have reduced recurrence risk. 



Protein Marker Can Predict 10-Year Radiotherapy Efficacy for DCIS

Despite a mandate to give patients timely and easy access to their radiology reports, many healthcare institutions have a built-in delay or embargo for releasing and making radiology reports available to patients. But, even that isn't a standardized practice.

Under the 21st Century Cures Act, providers are required to make electronic medical test reports, including those from radiologist, available to patients once they’re finalized. But, few facilities are following this requirement to the letter, according to a team of investigators from the Yale School of Medicine.

“Many [facilities] have made use of built-in delays or embargo periods, during which radiology reports were not released to patients, either because of technologic feasibility hurdles, or, in many cases, to give ordering clinicians the opportunity to first receive, review, and discuss the radiology report with their patients,” said the team led by Jonathan L. Mezrich, M.D., JD, MBA, assistant professor of emergency radiology.

To determine how prevalent the embargo period is, Mezrich’s team conducted a telephone survey of 70 “top hospitals” recognized in the 2019-2020 

 They published their results on May 4 in 

Based on the outcome of the survey, during which investigators posed as patients and family members interested in patient portal protocols, the team determined that 64 facilities (91 percent) offer online portals, and of those, 22 hospitals (34 percent) reported using a 1-to-3-day embargo period. Eight hospitals (13 percent) had 4-to-6-day delay, six facilities (9 percent) waited between 7-to-14 days, and 13 hospitals (20 percent) used an indefinite period. The remaining 15 institutions (23 percent) didn’t know.

5 Strategies to Streamline Patient Access to Radiology Reports

In addition, only 52 percent of hospitals confirmed they would send radiology reports to the referring clinician prior to making them available to the patient.

“However, there appears to be no standard with respect to embargo periods, with many institutions incorporating at least some period of delay into the process,” the team said. “Early patient access to their health information is valuable because it allows patients to better participate in their healthcare and to become their own advocates.”

It is possible that giving patients earlier access would reduce the likelihood that details found in the reports will be lost in the shuffle, they said. It could also improve compliance with follow-up recommendations – existing research shows that up to 15 percent of referring clinicians do not radiology reports, so they may never convey the radiologist’s guidance to the patient.

Still, the team said, there are several reasons why facilities could still resist giving patient’s earlier access to their radiology reports, and it is likely that these obstacles could fall into a patient safety, security, privacy, or feasibility exception under the Cures Act.

For example, hospitals could highlight these issues:

Early access isn’t feasible because they lack a streamlined system to make reports seamlessly available to patients.

Emotional harm to the patient who learns of a devastating diagnosis via an impersonal radiology report rather than an empathetic referring provider.

High-level medical language contained in radiology reports may be confusing to patients.

Early access limits a radiologists’ ability to make additions or corrections to reports before they are made available.

Security of electronically accessible reports cannot be guaranteed.

Still Mezrich’s team said, the march toward greater use of patient portals is continuing, so radiology must prepare for the high likelihood that patients will soon have open access to reports on their imaging findings.

“It is inevitable that radiologists will need to begin drafting reports for a lay audience, either through the use of structured reporting or decreased use of medical jargon, or both,” the team said. “Greater interface with patients through early receipt of radiology reports may even prove beneficial to the field of radiology, as patient will have a greater awareness of those providing their care; it may also decrease liability risks of lack of communication and may pave the way for other avenues of patient interaction.”

In addition, radiologists should build a habit of consulting with referring providers as promptly as possible to ensure that any findings are communicated in the safest most compassionate way.

Ultimately, the team said, radiology should view this continued push toward information transparency as a helpful move in healthcare.

“Given the benefits to patients, radiologists, and possibly institutions in providing early access, radiologists should embrace the final rule as a positive step in patient autonomy,” the team concluded.

Institutions still do not have a standardized way to make radiology reports available to patients, but providing earlier access could be beneficial for all parties involved.

To Embargo or Not to Embargo? No Consensus on Releasing Patient Radiology Reports

Women who have indeterminate BI-RADS© 3 or BI-RADS© 4 breast masses should undergo a diagnostic biopsy instead of having follow-up imaging if they are over age 50 or their breast ultrasound shows certain features, researchers have said.

Currently, there is little data about which BI-RADS© descriptors are most strongly associated with malignancy, so it can be difficult for providers to determine which women should receive BI-RADS© 3 (follow-up imaging) and which ones should be categorized as BI-RADS© 4 (diagnostic biopsy). Consequently, many breast cancers go unnoticed annually.

Investigators from Germany and the University of Virginia School of Medicine set out to reduce this number of missed cancers. In a study published May 4 in the 

they shared a new practical decision rule to help providers decide between categorizations.

“The new clinical decision rule states that a patient should undergo a diagnostic biopsy (BI-RADS© 4) instead of follow-up imaging (BI-RADS© 3) if the patient is 50 years or older or there is a presence of at least one of the following features: calcification, non-parallel orientation of mass, non-circumscribed margin, [or] posterior shadowing,” said the team led by Michael Golatta, M.D., senior consultant from the gynecology department at Heidelberg University in Germany.

For their study, the team enrolled 1,288 women, average age 46, between February 2016 and March 2019 who had been categorized as either BI-RADS© 3 or BI-RADS© 4 with a routine B-mode ultrasound exam with a linear 18 MHz transducer. The participants came from 12 study sites in seven countries (Austria, France, Germany, Japan, Portugal, The Netherlands, and the United States).

All images included multiple measurements, and all patients underwent histopathological confirmation. A team of three experts – a radiology professor, a breast diagnostics professor, and a senior physician specializing in breast diagnostics – assessed all the exams. Based on the histopathology, 368 of 1,288 masses (28.6 percent) were malignant, and the experts categorized 269 patients (20.9 percent) as BI-RADS© 3, 516 (40.1 percent) as BI-RADS© 4a, 299 (23.2 percent) as BI-RADS© 4b, and 204 (15.8 percent) as BI-RADS© 4c.

According to their assessments, spiculated margin, posterior shadowing, angular margin, non-parallel orientation, irregular shape, and calcification were most strongly associated with malignancy. Multivariate logistic regression also showed round mass shape; non-parallel mass orientation; non-circumscribed, indistinct margin; non-circumscribed, angular margin; non-circumscribed, microlobulated margin; posterior enhancement; calcification; and age over 50 years were also significantly associated with masses being cancerous.

Based on these findings, the team established their new clinical classification rule. In comparison to the three interpreting experts, they said, their rule demonstrated 97.3-percent sensitivity over the readers’ 78.8 percent-to-94.8 percent or the 59.2 percent of an existing classification rule. Specificity was comparable to the readers – 44.1 percent and 21.5 percent-to-44.9 percent, respectively, but it was much lower than the 82.7 percent achieved by the existing rule.

The new rule’s performance with false negatives and false positives was somewhat mixed, the team said. Compared to the readers, the new rule resulted in 23.7 percent fewer false positives and 56.5 percent fewer false negatives. However, against the existing rule, it resulted in 93.3 percent fewer false negatives and 323.3 percent more false positives.

“Although the high negative-predictive value is an important finding (very few women with cancer are missed), the positive-predictive value shows that this decision rule to differentiate BI-RADS© 3 or 4 breast masses is not yet optimal (many women may still undergo unnecessary biopsies despite having benign breast masses,” the team said. “Findings the optimal balance between an aggressive biopsy strategy and a conservative follow-up strategy is challenging and an ongoing issue in breast cancer care.”

The team noted that their results could be limited because the patient population was restricted to a group of pre-selected women who only had indeterminate BI-RADS© 3 and BI-RADS© 4 masses. As such, their finding may not be readily applicable to women with BI-RADS© 2 or BI-RADS© 5 masses.

Classification leads to fewer missed breast cancers.

New Clinical Rule Helps Distinguish Between BI-RADS 3 and 4 on Ultrasound

 Bird-beak narrowing as seen on this barium swallow study. The absence of air in the expected location of the gastric bubble on frontal radiograph is also seen here.

 There is often loss of esophageal peristalsis and loss of relaxation of the LES – lower esophageal sphincter. As a result there is an obstructive process resulting in food stasis and marked proximal dilatation of the esophagus. The differential diagnosis is secondary achalasia or pseudochalasia from possible malignancy is also a diagnostic consideration.

What is causing this appearance on this barium study?

Image IQ Quiz: What Do You See on This Barium Study?

Cloud-based medical image management company Ambra Health announced Tuesday it will partner with the vendor neutral artificial intelligence (AI) platform Arterys. It’s a move that will streamline interoperability and accelerate the use of AI applications, the companies said.

“We’re making AI real by improving the physician experience,” said John Axerio-Cilies, chief executive officer of Arterys. “We are increasing diagnosis, treatment accuracy, and ultimately outcomes that matter to patients and providers.”

Columns from Morris Panner, Ambra Health CEO

This partnership brings together Arterys’ seven AI solutions that have been cleared by the U.S. Food & Drug Administration, including Cardio AI, Lung AI, and Neuro AI, with Ambra’s interoperable, customizable cloud platform that consolidates multiple imaging systems that allows for secure access to imaging data anywhere, anytime.

Bringing together Arterys’ AI applications and Ambra’s platform opens the door for improved research and development, as well as patient care, said Ambra officials.

“Arterys has demonstrated that AI has rapidly moved from theory to practice. But, in order for AI programs to be effective, imaging data can’t operate in silos or disparate systems,” said Andrew Duckworth, Ambra Health vice president of business development. “By partnering with Arterys, we’re making it seamless for physicians to layer on innovative AI solutions to their existing Ambra cloud technology.”

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Collaboration paves the way for improved interoperability.

Ambra Health-Arterys Partnership Accelerates AI

Women who undergo annual screening mammography beginning at age 40 have lower-stage breast cancer at diagnosis and have fewer interval cancers that women who have biennial or non-annual screenings.

Amidst the ongoing debate around at what age and at what interval women should have mammograms, these findings support earlier and more frequent screenings.

“Despite the large number of lives saved because of cancer detection with screening mammography, controversy persists regarding screening frequency for women at average risk for breast cancer,” said a team led by Mark A. Helvie, M.D., FACR, radiology professor and director of breast imaging at the University of Michigan Rogel Cancer Center. “In this study, among all women and among post-menopausal women analyzed separately, annual screening was associated with lower [American Joint Committee on Cancer (AJCC)] stage, fewer interval cancers, and smaller mean tumor size compared with biennial or non-annual screening.”

The multi-institutional team published their findings in the May 6 

Currently, there is little consensus about when women should begin mammography screening. Recommendations range from annual screening beginning at age 40 – supported by both the American College of Radiology (ACR) and the National Comprehensive Cancer Network (NCCN) – to biennial screening for women ages 50 to 74 proposed by the U.S. Preventive Services Task Force.

To offer some clarity on which screening interval offers the best performance, Helvie’s team examined screening mammography records of 245 women ages 40-to-84 scanned between Jan. 1, 2016, and Dec. 31, 2017, who had mammographically detectable or clinically palpable interval primary breast cancer. Of the group, 200 (81.2 percent) had annual screening (every nine-to-15 months), 32 (13.1 percent) had biennial scans (every 21-to-27 months), and 13 (5.3 percent) had triennial (every 33-to-39 months) screening. Together, biennial and triennial screenings were considered non-annual.

Based on the analysis of 14 fellowship-trained breast radiologists, the team determined that annual screening offered women the most benefit. For women of all ages, annual screening was associated with fewer late-stage cancer presentations, a lower likelihood of interval cancers, and smaller average tumor diameter.

These findings held true for post-menopausal women, as well. Of the 191 post-menopausal women included in the study, those who were screened annually had less late-stage cancer, fewer interval cancers, and small average tumor diameters. These outcomes are important, the team noted, because previous research has not identified these benefits in this patient group.

Screening Outcomes for Post-Menopausal Women

The team noted that interval cancers have a two-fold higher hazard ratio for death than screening-detected cancers. In addition, they said, larger tumor size is an independent predictor of increased mortality.

The team found no statistically significant differences in the frequency of axillary lymph node positivity among interval groups, as well as no statistical differences in pathologic diagnosis. Also, while not statistically significant, annually screened women were less likely to undergo any axillary nodal surgery, showed less frequency use of chemotherapy, and used hormone therapy less frequently. Biennially- and non-annually screened women demonstrated greater use of axillary lymph node dissection.

“Our data show that breast cancers diagnosed in the setting of annual screening require less extensive treatment, which is not surprising given the lower AJCC stage, fewer interval cancers, and smaller mean tumor size,” the team said. “The results of this study support the recommendation for annual screening mammography for pre- and post-menopausal patients, consistent with annual screening recommendations by the ACR and the NCCN, which recommend screening initiation at age 40-years-old.”

Both pre- and post-menopausal women who undergo annual screening mammography have fewer late-stage breast cancer diagnoses, fewer interval cancers, and smaller average tumor size.

Annual Mammography Screening Offers Women of All Ages Same Benefits

Adding amino acid PET to contrast-enhanced MRI imaging can help radiologists better determine whether a patient has suffered a recurrence of a brain metastasis and how well he or she is responding to treatment.

Although new treatments for brain metastases, such as immune checkpoint inhibitors (ICI) and targeted therapies (TT), are effective, assessing just how well they are working in an individual patient can be difficult. The results produced by contrast-enhanced MRI can be variable, said a team of German investigators.

Consequently, there is a need for new assessment strategy, they said.

“Essentially, these new treatments have requirements of brain imaging which cannot be met by conventional MRI,” said Norbert Galldiks, M.D., a neurology professor, as well as a neurologist and neuro-oncologist at the University Hospital Cologne and Research Center in Juelich, Germany. “In our study, we tried to determine if adding 

F-FET PET could help to overcome some of these imaging challenges.”

Galldiks’ team published their findings recently in the 

PET/MRI Outperforms PET/CT in Cancer Imaging

For their retrospective study, the team enrolled 40 patients who had 107 brain metastases that were secondary to melanoma and small cell lung cancer. These individuals were treated with either ICI or TT alone or in combination with radiotherapy.

After radiosurgery concurrent with nivolumab in 59-year-old patient with melanoma BM (patient 1; Supplemental Tables 3 and 5), F-18 FET PET at follow-up 12 weeks after treatment initiation (bottom row) shows significant decrease of metabolic activity (TBRmean, ?28%) compared with baseline (top row), although MRI changes were consistent with progression according to iRANO criteria. Reduction of metabolic activity was associated with stable clinical course over 10 mo. CE = contrast-enhanced.

CREDIT: N. Galldiks et al., Research Center Juelich, Juelich, Germany.

F-FET PET scans to monitor their treatment efficacy between 2015 and 2019. In 27 patients, it was used to differentiate treatment-related changes from metastasis relapse after ICI or TT, and in 13 patients, it was performed for response assessment to both treatments, using baseline and follow-up scans.

Based on their analysis, the team determined that 

F-FET PET can correctly diagnose brain metastasis relapse and pinpoint which patients are responding to treatment and which are not. Specifically, they found a tumor-to-brain ratio threshold of 1.95 differentiated brain metastasis relapse from treatment-related changes with 85-percent accuracy. In addition, they saw that metabolic responders to ICI or TT on 

F-FET PET had significantly longer stable follow-up, and their time to peak also increased substantially, as well.

F-FET PET is beneficial in monitoring ICI- or TT-treated patients.

“In cases of ambiguous MRI findings, supplemental FET PET is helpful for treatment monitoring. It provides physicians with a longer time window for subsequent patient management and allows them to optimize the treatment strategy for each individual patient,” he said. “Since this approach is so accurate, it has the potential to influence clinical decision making. This may help to reduce the number of invasive procedures and limit over-treatment for a considerable number of seriously ill patients with brain metastases."

Adding 18F-FET PET to contrast-enhanced MRI can better determine which patients are responding well to immune checkpoint inhibitors or targeted therapies.

Annual Mammography Screening Offers Women of All Ages Same Benefits

PET Imaging Identifies Efficacy of New Brain Metastasis Treatments

Diagnostic Imaging's Weekly Scan: May 3 to May 7, 2021