Publications

2023

Bhadelia, Rafeeque A, Yu-Ming Chang, John N Oshinski, and Francis Loth. (2023) 2023. “Cerebrospinal Fluid Flow and Brain Motion in Chiari I Malformation: Past, Present, and Future.”. Journal of Magnetic Resonance Imaging : JMRI 58 (2): 360-78. https://doi.org/10.1002/jmri.28717.

Cranio-spinal volume and pressure changes associated with the cardiac-cycle and respiration are altered in Chiari I malformation (CMI) due to obstruction of cerebrospinal fluid (CSF) flow at the foramen magnum. With the introduction of motion-sensitive MRI sequences, it was envisioned that these could provide noninvasive information about volume-pressure dynamics at the cranio-cervical junction in CMI hitherto available only through invasive pressure measurements. Since the early 1990s, multiple studies have assessed CSF flow and brain motion in CMI. However, differences in design and varied approaches in the presentation of results and conclusions makes it difficult to fully comprehend the role of MR imaging of CSF flow and brain motion in CMI. In this review, a cohesive summary of the current status of MRI assessment of CSF flow and brain motion in CMI is presented. Simplified versions of the results and conclusions of previous studies are presented by dividing the studies in distinct topics: 1) comparing CSF flow and brain motion between healthy subjects (HS) and CMI patients (before and after surgery), 2) comparing CSF flow and brain motion to CMI severity and symptoms, and 3) comparing CSF flow and brain motion in CMI with and without syringomyelia. Finally, we will discuss our vision of the future directions of MR imaging in CMI patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: 5.

Bezuidenhout, Abraham F, Pei-Kang Wei, Deborah Burstein, Alexander Brook, Olga R Brook, Steven D Freedman, and Leo L Tsai. (2023) 2023. “Unexplained Acute Distal Pancreatitis: Association With Subsequent Diagnosis of Pancreatic Cancer.”. AJR. American Journal of Roentgenology 221 (2): 196-205. https://doi.org/10.2214/AJR.23.28999.

BACKGROUND. Distal pancreatitis is an atypical imaging subtype of acute pancreatitis involving only the pancreatic body and tail, the head being spared. If no cause is identified, suspicion of a small imaging-occult cancer may be warranted. OBJECTIVE. The purpose of this study was to determine the frequency of subsequently diagnosed pancreatic cancer in patients with unexplained acute distal pancreatitis and to compare this frequency to that found in patients with unexplained nondistal pancreatitis. METHODS. This retrospective study included patients who underwent contrast-enhanced CT between January 1, 2019, and December 31, 2020, that showed acute pancreatitis without identifiable explanation. Studies were classified as showing distal or nondistal acute pancreatitis on the basis of consensus. The Fisher exact test was used to compare the frequency of subsequent histologic diagnosis of pancreatic cancer between groups. Negative classification required 6 or more months of imaging follow-up and/or 12 or more months of clinical follow-up. Interreader agreement among seven readers of varying experience was assessed by Fleiss kappa. RESULTS. Among 215 patients with acute pancreatitis, 116 (54%) had no identifiable explanation and formed the study sample. A total of 100 of 116 (86%) patients (59 men, 41 women; mean age, 57 ± 18 [SD] years) had nondistal acute pancreatitis; 16 of 116 (14%) patients (10 men, six women; mean age, 66 ± 14 years) had distal acute pancreatitis. Among patients with nondistal pancreatitis, none were subsequently diagnosed with pancreatic cancer; 62 had sufficient follow-up (median, 2.5 years) to be classified as having negative follow-up for pancreatic cancer. Among patients with distal pancreatitis, nine were subsequently diagnosed with pancreatic cancer (median interval to suspected cancer on subsequent CT, 174 days); five had sufficient follow-up (median, 3.1 years) to be classified as having negative follow-up for pancreatic cancer. The frequency of pancreatic cancer was higher (p < .001) in patients with distal pancreatitis (9/14 [64%; 95% CI, 35-87%]) than in with those with nondistal pancreatitis (0/62 [0%; 95% CI, 0-6%]). Interreader agreement on classification of distal versus nondistal pancreatitis was almost perfect (κ = 0.81). CONCLUSION. Distal pancreatitis without identifiable cause on CT is an uncommon but unique imaging subtype of acute pancreatitis that is associated with a high frequency of pancreatic cancer. CLINICAL IMPACT. In patients with acute distal pancreatitis without identifiable cause, endoscopic ultrasound-guided biopsy should be considered to evaluate for an underlying small cancer.

Dave, Priya, Olga R Brook, Alexander Brook, Ammar Sarwar, and Bettina Siewert. (2023) 2023. “Moral Distress in Radiology: Frequency, Root Causes, and Countermeasures-Results of a National Survey.”. AJR. American Journal of Roentgenology 221 (2): 249-57. https://doi.org/10.2214/AJR.22.28968.

BACKGROUND. A major cause of burnout is moral distress: when one knows the right course of action but institutional constraints make the right course impossible to pursue. OBJECTIVE. The purpose of this study was to assess the frequency and severity with which radiologists experience moral distress and to explore moral distress's root causes and countermeasures. METHODS. This study entailed a national survey that evaluated moral distress in radiology. The survey incorporated the validated Moral Distress Scale for Health Care Professionals, along with additional questions. After the scale was modified for applicability to radiology, respondents were asked to assess 16 clinical scenarios in terms of frequency and severity of moral distress. On May 10, 2022, the survey was sent by e-mail to 425 members of radiology practices included on a national radiology society's quality-and-safety LISTSERV. The Measure of Moral Distress for Health Care Professionals (MMD-HP) score was calculated for each respondent as a summary measure of distress across scenarios (maximum possible score, 256). RESULTS. After 12 surveys with incomplete data were excluded, the final analysis included 93 of 425 respondents (22%). A total of 91 of 93 respondents (98%) experienced at least some moral distress for at least one scenario. A total of 17 of 93 respondents (18%) had left a clinical position due to moral distress; 26 of 93 (28%) had considered leaving a clinical position due to moral distress but did not leave. The mean MMD-HP score was 73 ± 51 (SD) for those who had left, 89 ± 47 for those who had considered leaving but did not leave, and 39 ± 35 for those who had never considered leaving (p < .001). A total of 41 of 85 respondents (48%) thought that the COVID-19 pandemic had influenced their moral distress level. Across respondents, the three scenarios with highest moral distress were related to systemic causes (higher case volume than could be read safely, high case volume preventing teaching residents, and lack of administrative action or support). The countermeasure most commonly selected to alleviate moral distress was educating leadership about sources of moral distress (71%). CONCLUSION. Moral distress is prevalent in radiology, typically relates to systemic causes, and is a reported contributor to radiologists changing jobs. CLINICAL IMPACT. Urgent action by radiology practice leadership is required to address moral distress, as radiologists commonly practice in environments contradictory to their core values as physicians.

Vandergrift, Lindsey A, Nanbu Wang, Miry Zhu, Bailing Li, Shuyi Chen, Piet Habbel, Johannes Nowak, et al. (2023) 2023. “13 C NMR Quantification of Polyamine Syntheses in Rat Prostate.”. NMR in Biomedicine 36 (8): e4931. https://doi.org/10.1002/nbm.4931.

Currently, many prostate cancer patients, detected through the prostate specific antigen test, harbor organ-confined indolent disease that cannot be differentiated from aggressive cancer according to clinically and pathologically known measures. Spermine has been considered as an endogenous inhibitor for prostate-confined cancer growth and its expression has shown correlation with prostate cancer growth rates. If established clinically, measurements of spermine bio-synthesis rates in prostates may predict prostate cancer growth and patient outcomes. Using rat models, we tested the feasibility of quantifying spermine bio-synthesis rates with 13 C NMR. Male Copenhagen rats (10 weeks, n = 6) were injected with uniformly 13 C-labeled L-ornithine HCl, and were sacrificed in pairs at 10, 30, and 60 min after injection. Another two rats were injected with saline and sacrificed at 30 min as controls. Prostates were harvested and extracted with perchloric acid and the neutralized solutions were examined by 13 C NMR at 600 MHz. 13 C NMR revealed measurable ornithine, as well as putrescine-spermidine-spermine syntheses in rat prostates, allowing polyamine bio-synthetic and ornithine bio-catabolic rates to be calculated. Our study demonstrated the feasibility of 13 C NMR for measuring bio-synthesis rates of ornithine to spermine enzymatic reactions in rat prostates. The current study established a foundation upon which future investigations of protocols that differentiate prostate cancer growth rates according to the measure of ornithine to spermine bio-synthetic rates may be developed.

Ivanovic, Vladimir, Alireza Paydar, Yu-Ming Chang, Kenneth Broadhead, David Smullen, Andrew Klein, and Lotfi Hacein-Bey. (2023) 2023. “Impact of Shift Volume on Neuroradiology Diagnostic Errors at a Large Tertiary Academic Center.”. Academic Radiology 30 (8): 1584-88. https://doi.org/10.1016/j.acra.2022.08.035.

BACKGROUND AND PURPOSE: Medical errors can result in significant morbidity and mortality. The goal of our study is to evaluate correlation between shift volume and errors made by attending neuroradiologists at an academic medical center, using a large data set.

MATERIALS AND METHODS: CT and MRI reports from our Neuroradiology Quality Assurance database (years 2014 - 2020) were searched for attending physician errors. Data were collected on shift volume, category of missed findings, error type, interpretation setting, exam type, clinical significance.

RESULTS: 654 reports contained diagnostic error. There was a significant difference between mean volume of interpreted studies on shifts when an error was made compared with shifts in which no error was documented (46.58 (SD=22.37) vs 34.09 (SD=18.60), p<0.00001); and between shifts when perceptual error was made compared with shifts when interpretive errors were made (49.50 (SD=21.9) vs 43.26 (SD=21.75), p=0.0094). 59.6% of errors occurred in the emergency/inpatient setting, 84% were perceptual and 91.1% clinically significant. Categorical distribution of errors was: vascular 25.8%, brain 23.4%, skull base 13.8%, spine 12.4%, head/neck 11.3%, fractures 10.2%, other 3.1%. Errors were detected most often on brain MRI (25.4%), head CT (18.7%), head/neck CTA (13.8%), spine MRI (13.7%).

CONCLUSION: Errors were associated with higher volume shifts, were primarily perceptual and clinically significant. We need National guidelines establishing a range of what is a safe number of interpreted cross-sectional studies per day.

Samman, Mohamad Motaz F Al, Alaaddin Ibrahimy, Blaise Simplice Talla Nwotchouang, John N Oshinski, Daniel L Barrow, Philip A Allen, Rouzbeh Amini, Rafeeque A Bhadelia, and Francis Loth. (2023) 2023. “The Relationship Between Imbalance Symptom and Cardiac Pulsation Induced Mechanical Strain in the Brainstem and Cerebellum for Chiari Malformation Type I.”. Journal of Biomechanical Engineering 145 (8). https://doi.org/10.1115/1.4062723.

Chiari malformation Type I (CMI) is known to have an altered biomechanical environment for the brainstem and cerebellum; however, it is unclear whether these altered biomechanics play a role in the development of CMI symptoms. We hypothesized that CMI subjects have a higher cardiac-induced strain in specific neurological tracts pertaining to balance, and postural control. We measured displacement over the cardiac cycle using displacement encoding with stimulated echoes magnetic resonance imaging in the cerebellum, brainstem, and spinal cord in 37 CMI subjects and 25 controls. Based on these measurements, we computed strain, translation, and rotation in tracts related to balance. The global strain on all tracts was small (<1%) for CMI subject and controls. Strain was found to be nearly doubled in three tracts for CMI subjects compared to controls (p < 0.03). The maximum translation and rotation were ∼150 μm and ∼1 deg, respectively and 1.5-2 times greater in CMI compared to controls in four tracts (p < 0.005). There was no significant difference between strain, translation, and rotation on the analyzed tracts in CMI subjects with imbalance compared to those without imbalance. A moderate correlation was found between cerebellar tonsillar position and strain on three tracts. The lack of statistically significant difference between strain in CMI subjects with and without imbalance could imply that the magnitude of the observed cardiac-induced strain was too small to cause substantial damage to the tissue (<1%). Activities such as coughing, or Valsalva may produce a greater strain.

Hogstrom, Jenny M, Kayla A Cruz, Laura M Selfors, Madelyn N Ward, Tejas S Mehta, Naama Kanarek, Jordana Philips, et al. (2023) 2023. “Simultaneous Isolation of Hormone Receptor-Positive Breast Cancer Organoids and Fibroblasts Reveals Stroma-Mediated Resistance Mechanisms.”. The Journal of Biological Chemistry 299 (8): 105021. https://doi.org/10.1016/j.jbc.2023.105021.

Recurrent hormone receptor-positive (HR+) breast cancer kills more than 600,000 women annually. Although HR+ breast cancers typically respond well to therapies, approximately 30% of patients relapse. At this stage, the tumors are usually metastatic and incurable. Resistance to therapy, particularly endocrine therapy is typically thought to be tumor intrinsic (e.g., estrogen receptor mutations). However, tumor-extrinsic factors also contribute to resistance. For example, stromal cells, such as cancer-associated fibroblasts (CAFs), residing in the tumor microenvironment, are known to stimulate resistance and disease recurrence. Recurrence in HR+ disease has been difficult to study due to the prolonged clinical course, complex nature of resistance, and lack of appropriate model systems. Existing HR+ models are limited to HR+ cell lines, a few HR+ organoid models, and xenograft models that all lack components of the human stroma. Therefore, there is an urgent need for more clinically relevant models to study the complex nature of recurrent HR+ breast cancer, and the factors contributing to treatment relapse. Here, we present an optimized protocol that allows a high take-rate, and simultaneous propagation of patient-derived organoids (PDOs) and matching CAFs, from primary and metastatic HR+ breast cancers. Our protocol allows for long-term culturing of HR+ PDOs that retain estrogen receptor expression and show responsiveness to hormone therapy. We further show the functional utility of this system by identifying CAF-secreted cytokines, such as growth-regulated oncogene α , as stroma-derived resistance drivers to endocrine therapy in HR+ PDOs.

Musa, Balowa, Jared Mark Alswang, Rose Di Ioia, Lydia Grubic, Azza Naif, Erick Michael Mbuguje, Victoria Vuong, et al. (2023) 2023. “Uterine Artery Embolization in Tanzania: A Procedure With Major Public Health Implications.”. CVIR Endovascular 6 (1): 40. https://doi.org/10.1186/s42155-023-00384-9.

BACKGROUND: The burden of uterine fibroids is substantial in sub-Saharan Africa (SSA), with up to 80% of black women harboring them in their lifetime. While uterine artery embolization (UAE) has emerged as an effective alternative to surgery to manage this condition, the procedure is not available to the vast majority of women living in SSA due to limited access to interventional radiology (IR) in the region. One of the few countries in SSA now offering UAE in a public hospital setting is Tanzania. This study aims to assess the safety and effectiveness of UAE in this new environment.

METHODS: From June 2019 to July 2022, a single-center, retrospective cohort study was conducted at Tanzania's first IR service on all patients who underwent UAE for the management of symptomatic fibroids or adenomyosis. Patients were selected for the procedure based on symptom severity, imaging findings, and medical management failure. Procedural technical success and adverse events were recorded for all UAEs. Self-reported symptom severity and volumetric response on imaging were compared between baseline and six-months post-procedure using paired sample t-tests.

RESULTS: During the study period, 92.1% (n = 35/38) of patients underwent UAE for the management of symptomatic fibroids and 7.9% (n = 3/38) for adenomyosis. All (n = 38/38) were considered technically successful and one minor adverse event occurred (2.7%). Self-reported symptom-severity scores at six-months post-procedure decreased in all categories: abnormal uterine bleeding from 8.8 to 3.1 (-5.7), pain from 6.7 to 3.2 (-3.5), and bulk symptoms from 2.8 to 1 (-1.8) (p < 0.01). 100% of patients reported satisfaction with outcomes. Among the nine patients with follow-up imaging, there was a mean volumetric decrease of 35.5% (p = 0.109).

CONCLUSIONS: UAE for fibroids and adenomyosis can be performed with high technical success and low complication rates in a low-resource setting like Tanzania, resulting in significant symptom relief for patients. Building capacity for UAE has major public health implications not only for fibroids and adenomyosis, but can help address the region's leading cause of maternal mortality, postpartum hemorrhage.

Zhang, Zongpai, Huiyuan Yang, Yanchen Guo, Nicolas R Bolo, Matcheri Keshavan, Eve DeRosa, Adam K Anderson, David C Alsop, Lijun Yin, and Weiying Dai. (2023) 2023. “Affine Image Registration of Arterial Spin Labeling MRI Using Deep Learning Networks.”. NeuroImage 279: 120303. https://doi.org/10.1016/j.neuroimage.2023.120303.

Convolutional neural networks (CNN) have demonstrated good accuracy and speed in spatially registering high signal-to-noise ratio (SNR) structural magnetic resonance imaging (sMRI) images. However, some functional magnetic resonance imaging (fMRI) images, e.g., those acquired from arterial spin labeling (ASL) perfusion fMRI, are of intrinsically low SNR and therefore the quality of registering ASL images using CNN is not clear. In this work, we aimed to explore the feasibility of a CNN-based affine registration network (ARN) for registration of low-SNR three-dimensional ASL perfusion image time series and compare its performance with that from the state-of-the-art statistical parametric mapping (SPM) algorithm. The six affine parameters were learned from the ARN using both simulated motion and real acquisitions from ASL perfusion fMRI data and the registered images were generated by applying the transformation derived from the affine parameters. The speed and registration accuracy were compared between ARN and SPM. Several independent datasets, including meditation study (10 subjects × 2), bipolar disorder study (26 controls, 19 bipolar disorder subjects), and aging study (27 young subjects, 33 older subjects), were used to validate the generality of the trained ARN model. The ARN method achieves superior image affine registration accuracy (total translation/total rotation errors of ARN vs. SPM: 1.17 mm/1.23° vs. 6.09 mm/12.90° for simulated images and reduced MSE/L1/DSSIM/Total errors of 18.07% / 19.02% / 0.04% / 29.59% for real ASL test images) and 4.4 times (ARN vs. SPM: 0.50 s vs. 2.21 s) faster speed compared to SPM. The trained ARN can be generalized to align ASL perfusion image time series acquired with different scanners, and from different image resolutions, and from healthy or diseased populations. The results demonstrated that our ARN markedly outperforms the iteration-based SPM both for simulated motion and real acquisitions in terms of registration accuracy, speed, and generalization.

Lewis, Paul Bennett, Resmi Ann Charalel, Aliaksei Salei, Andrew J Cantos, Greg J Dubel, Michael T Kassin, Tushar Garg, et al. (2023) 2023. “Challenges, Barriers, and Successes Of Standardized Report Templates: Results of a Society of Interventional Radiology Survey.”. Journal of Vascular and Interventional Radiology : JVIR 34 (12): 2218-2223.e10. https://doi.org/10.1016/j.jvir.2023.08.020.

Registry data are being increasingly used to establish treatment guidelines, set benchmarks, allocate resources, and make payment decisions. Although many registries rely on manual data entry, the Society of Interventional Radiology (SIR) is using automated data extraction for its VIRTEX registry. This process relies on participants using consistent terminology with highly structured data in physician-developed standardized reports (SR). To better understand barriers to adoption, a survey was sent to 3,178 SIR members. Responses were obtained from 451 interventional radiology practitioners (14.2%) from 92 unique academic and 151 unique private practices. Of these, 75% used structured reports and 32% used the SIR SR. The most common barriers to the use of these reports include SR length (35% of respondents), lack of awareness about the SR (31%), and lack of agreement on adoption within practices (27%). The results demonstrated insights regarding barriers in the use and/or adoption of SR and potential solutions.