Publications

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.

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.

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.

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.

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.

OBJECTIVES: To determine the factors that affect successful ultrasound-guided biopsy of liver lesions and build a model predicting feasibility of US-guided liver biopsy.

METHODS: This is IRB-approved HIPAA-compliant retrospective review of consecutive ultrasound-guided targeted liver biopsies performed or attempted between 1/2018 and 9/2020 at a single tertiary academic institution with a total of 501 patients included. Mann-Whitney and chi-square tests were used to compare continuous and categorical variables, respectively. Logistic regression model was built to predict feasibility of successful ultrasound-guided biopsy.

RESULTS: Liver lesion biopsy was successfully performed with US guidance in 429/501 (86%) patients. Lesions not amenable for US biopsy were smaller (median size 1.6 cm vs 3.3 cm, p < 0.0001) and deeper within the liver (median depth 9.0 cm vs 5.8 cm, p < 0.0001). The technical success rate was lowest for lesions in segment II (40/53, 75%), while lesions in segment IVb (87/91, 96%) had highest success rate (p < 0.003). US targeting in patients with 1 or 2 lesions was less feasible than in patients with 3 or more lesions, 126/180 (70%) vs. 303/321 (94%), (p < 0.0001). Model including lesion size, depth, location, and number of lesions predicts feasibility of US-guided biopsy with Area under the ROC curve (AUC) = 0.92.

CONCLUSIONS: Linear logistic regression model that includes lesion size, depth and location, and number of lesions is highly successful in predicting feasibility of ultrasound-guided biopsy for liver lesions. Smaller lesions, deeper lesions, and lesions in segment II and VIII in patients with less than 3 lesions were less feasible for ultrasound-guided biopsy of liver lesions.

The purpose of this study is to compare the subjective and objective quality and confidence between conventional angiography with cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI) for the preoperative evaluation of potential donors for living donor liver transplant. Seventeen patients undergoing preoperative donor evaluation for living donor liver transplantation that underwent angiography with CBCT and contrast-enhanced MRI for evaluation of hepatic vascular anatomy were included in the study. Four attending radiologists interpreted anonymized, randomized angiography with CBCT images and MRIs, rating the diagnostic quality and confidence of their interpretation (on a 3-point scale) for each element, as well as clinically relevant measurements. Overall, the readers rated the quality of angiography with CBCT to be higher than that of MRI (median [interquartile range] = 3 (2, 3) vs. 2 (1-3), p < 0.001) across all patients. Readers of angiography with CBCT had more confidence in their interpretations as an average of all elements evaluated than the MRI readers (3 (3) vs. 3 (2, 3), p < 0.001). When the same reader interpreted both MRI and CBCT, the right hepatic artery diameter (3.8 mm ± 0.72 mm vs. 4.5 mm ± 1.2 mm, p < 0.005) and proper hepatic artery diameter (4.43 mm ± 0.98 mm vs. 5.4 mm ± 1.05 mm, p < 0.003) were significantly different between MRI and CBCT. There was poor interrater reliability for determining segment IV arterial supply for both modalities (κ < 0.2). Angiography with CBCT provides higher subjective diagnostic quality and greater radiologist confidence than MRI. The difference in measurements between CBCT and MRI when the same reader reads both studies suggests CBCT adds additional information over MRI evaluation alone.

This study aimed to evaluate the geographic patient profile of a country's first interventional radiology (IR) service in sub-Saharan Africa. From October 2018 to August 2022, travel time (1,339 patients) and home region (1,184 patients) were recorded from 1,434 patients who underwent IR procedures at Tanzania's largest referral center. Distances traveled by road were calculated from the administrative capital of each region using a web mapping platform (google.com/maps). The effect of various factors on distance and time traveled were assessed. Patients from all 31 regions in Tanzania underwent IR procedures. The mean and maximum calculated distance traveled by patients were 241.6 km and 1,387 km, respectively (Sk2 = 1.66); 25.0% of patients traveled for over 6 hours for their procedure. Patients traveled furthest for genitourinary procedures (mean = 293.4 km) and least for angioplasty and stent placement (mean = 123.9 km) (P < .001). To increase population access and reduce travel times, geographic data should be used to decentralize services.

BACKGROUND. Numerous studies have explored factors associated with diagnostic errors in neuroradiology; however, large-scale multivariable analyses are lacking. OBJECTIVE. The purpose of this study was to evaluate associations of interpretation time, shift volume, care setting, day of week, and trainee participation with diagnostic errors by neuroradiologists at a large academic medical center. METHODS. This retrospective case-control study using a large tertiary-care academic medical center's neuroradiology quality assurance database evaluated CT and MRI examinations for which neuroradiologists had assigned RADPEER scores. The database was searched from January 2014 through March 2020 for examinations without (RADPEER score of 1) or with (RADPEER scores of 2a, 2b, 3a, 3b, or 4) diagnostic error. For each examination with error, two examinations without error were randomly selected (unless only one examination could be identified) and matched by interpreting radiologist and examination type to form case and control groups. Marginal mixed-effects logistic regression models were used to assess associations of diagnostic error with interpretation time (number of minutes since the immediately preceding report's completion), shift volume (number of examinations interpreted during the shift), emergency/inpatient setting, weekend interpretation, and trainee participation in interpretation. RESULTS. The case group included 564 examinations in 564 patients (mean age, 50.0 ± 25.0 [SD] years; 309 men, 255 women); the control group included 1019 examinations in 1019 patients (mean age, 52.5 ± 23.2 years; 540 men, 479 women). In the case versus control group, mean interpretation time was 16.3 ± 17.2 [SD] minutes versus 14.8 ± 16.7 minutes; mean shift volume was 50.0 ± 22.1 [SD] examinations versus 45.4 ± 22.9 examinations. In univariable models, diagnostic error was associated with shift volume (OR = 1.22, p < .001) and weekend interpretation (OR = 1.60, p < .001) but not interpretation time, emergency/inpatient setting, or trainee participation (p > .05). However, in multivariable models, diagnostic error was independently associated with interpretation time (OR = 1.18, p = .003), shift volume (OR = 1.27, p < .001), and weekend interpretation (OR = 1.69, p = .02). In subanalysis, diagnostic error showed independent associations on weekdays with interpretation time (OR = 1.18, p = .003) and shift volume (OR = 1.27, p < .001); such associations were not observed on weekends (interpretation time: p = .62; shift volume: p = .58). CONCLUSION. Diagnostic errors in neuroradiology were associated with longer interpretation times, higher shift volumes, and weekend interpretation. CLINICAL IMPACT. These findings should be considered when designing work-flow-related interventions seeking to reduce neuroradiology interpretation errors.

PURPOSE: To demonstrate the bias in quantitative MT (qMT) measures introduced by the presence of dipolar order and on-resonance saturation (ONRS) effects using magnetization transfer (MT) spoiled gradient-recalled (SPGR) acquisitions, and propose changes to the acquisition and analysis strategies to remove these biases.

METHODS: The proposed framework consists of SPGR sequences prepared with simultaneous dual-offset frequency-saturation pulses to cancel out dipolar order and associated relaxation (T1D ) effects in Z-spectrum acquisitions, and a matched quantitative MT (qMT) mathematical model that includes ONRS effects of readout pulses. Variable flip angle and MT data were fitted jointly to simultaneously estimate qMT parameters (macromolecular proton fraction [MPF], T2,f , T2,b , R, and free pool T1 ). This framework is compared with standard qMT and investigated in terms of reproducibility, and then further developed to follow a joint single-point qMT methodology for combined estimation of MPF and T1 .

RESULTS: Bland-Altman analyses demonstrated a systematic underestimation of MPF (-2.5% and -1.3%, on average, in white and gray matter, respectively) and overestimation of T1 (47.1 ms and 38.6 ms, on average, in white and gray matter, respectively) if both ONRS and dipolar order effects are ignored. Reproducibility of the proposed framework is excellent (ΔMPF = -0.03% and ΔT1  = -19.0 ms). The single-point methodology yielded consistent MPF and T1 values with respective maximum relative average bias of -0.15% and -3.5 ms found in white matter.

CONCLUSION: The influence of acquisition strategy and matched mathematical model with regard to ONRS and dipolar order effects in qMT-SPGR frameworks has been investigated. The proposed framework holds promise for improved accuracy with reproducibility.