Publications

2023

Ramos, Francisco, Ruslan Korets, Aaron Fleishman, Sumedh Kaul, Michael Johnson, Jesse L Wei, Aria F Olumi, Leo L Tsai, and Boris Gershman. (2023) 2023. “Comparative Effectiveness of Magnetic Resonance Imaging-Ultrasound Fusion Versus In-Bore Magnetic Resonance Imaging-Targeted Prostate Biopsy.”. Urology 171: 164-71. https://doi.org/10.1016/j.urology.2022.09.016.

OBJECTIVE: To examine the comparative effectiveness of magnetic resonance imaging-ultrasound (MRI-U/S) fusion biopsy and in-bore MRI-targeted biopsy.

METHODS: We identified men aged 18-89 with a diagnosis of elevated prostate specific antigen (PSA) or Gleason 6 prostate cancer on active surveillance who underwent MRI-U/S fusion prostate biopsy (12-core + targeted) in the office or in-bore MRI-targeted biopsy (MRI-IB; targeted only). The cancer detection rate (CDR; Gleason 6-10) and clinically significant CDR (csCDR; Gleason 7-10) were compared across biopsy techniques, adjusted for patient and radiographic features.

RESULTS: A total of 280 patients (346 lesions) were included, of whom 23.9% were on active surveillance for Gleason 6 prostate cancer. In the per-patient analyses, there was no statistically significant difference in adjusted overall CDR (64.1% vs 54.2%; P = .24) or csCDR (36.5% vs 37.9%; P = .85) between MRI-U/S and MRI-IB biopsy. In the per-lesion analyses, there was no statistically significant difference in adjusted overall CDR (45.7% vs 50.1%; P = .49) between MRI-U/S and MRI-IB biopsy, but MRI-IB biopsy was associated with a higher csCDR than MRI-U/S biopsy (32.8% vs 21.4%; P = .02).

CONCLUSION: We observed no statistically significant differences in cancer detection rates between MRI-U/S fusion biopsy and MRI-IB biopsy in per-patient analyses. However, MRI-IB biopsy was associated with higher csCDR when considering targeted biopsy cores only. These results suggest that systematic cores should be obtained when performing MRI-U/S fusion biopsy.

Kim, Wonsuk, Kevin Sun, Justin W Kung, and Jim S Wu. (2023) 2023. “CT-Guided Core Needle Biopsy of Nonspinal Bone Lesions: Comparison of Occult and Visible Bone Lesions.”. AJR. American Journal of Roentgenology 220 (1): 104-14. https://doi.org/10.2214/AJR.22.27842.

BACKGROUND. CT guidance may be used for biopsy of indeterminate bone lesions detected by MRI or PET/CT that are not visible (i.e., occult) on CT owing to equipment-, patient-, and operator-related factors. OBJECTIVE. The purpose of this study was to assess diagnostic yield (DY) and diagnostic performance of CT-guided core needle biopsy (CNB) of occult nonspinal bone lesions and to identify the most common benign and malignant diagnoses for occult lesions undergoing CNB. METHODS. This retrospective study included 1033 adult patients who underwent CT-guided nonspinal bone CNB between January 2004 and December 2020. Lesions were classified as occult or visible on CT; biopsies of occult lesions were performed by targeting anatomic landmarks using prebiopsy MRI or PET/CT. Pathologic results of CNB were classified as diagnostic or nondiagnostic to calculate DY of CNB. For nondiagnostic CNBs, final diagnoses were established by subsequent pathologic, clinical, and imaging follow-up. RESULTS. The sample included 70 patients with occult lesions (mean age, 56.8 years; 38 women, 32 men) and 963 patients with visible lesions (mean age, 59.6 years; 475 women, 488 men). Malignancy rate was lower for occult than for visible lesions (42.9% vs 60.9%, p = .004). DY was lower for occult than for visible lesions (37.1% vs 76.9%, p < .001). Diagnostic performance for detecting malignancy on the basis of final diagnoses was lower for occult than for visible lesions in terms of sensitivity (76.7% vs 93.7%, p = .003), specificity (7.9% vs 56.5%, p < .001), and accuracy (38.2% vs 80.0%, p < .001). Final diagnoses among malignant occult and visible lesions included metastasis (frequencies of 63.3% vs 65.4%), leukemia/lymphoma (33.3% vs 11.6%), and myeloma (3.3% vs 10.4%); final diagnoses among benign occult and visible lesions included red marrow (34.2% vs 8.2%), reactive marrow (26.3% vs 11.8%), and fracture (18.4% vs 3.8%). Occult lesions detected by MRI versus PET/CT had lower malignancy rate (39.3% vs 68.0%, p = .03) and lower DY (30.4% vs 60.0%, p = .01). CONCLUSION. At CT-guided CNB, malignancy rate and DY are lower for occult than for visible lesions. Leukemia/lymphoma and red marrow are more common among occult than visible lesions. CLINICAL IMPACT. Understanding these characteristics can help guide radiologists', referring providers', and patients' expectations when CNB of occult bone lesions is requested and performed.

Salehi, Betsa Parsai, Robert Carson Sibley, Rosie Friedman, Geunwon Kim, Dhruv Singhal, Andreas Markus Loening, and Leo L Tsai. (2023) 2023. “MRI of Lymphedema.”. Journal of Magnetic Resonance Imaging : JMRI 57 (4): 977-91. https://doi.org/10.1002/jmri.28496.

Lymphedema is a devastating disease that has no cure. Management of lymphedema has evolved rapidly over the past two decades with the advent of surgeries that can ameliorate symptoms. MRI has played an increasingly important role in the diagnosis and evaluation of lymphedema, as it provides high spatial resolution of the distribution and severity of soft tissue edema, characterizes diseased lymphatic channels, and assesses secondary effects such as fat hypertrophy. Many different MR techniques have been developed for the evaluation of lymphedema, and the modality can be tailored to suit the needs of a lymphatic clinic. In this review article we provide an overview of lymphedema, current management options, and the current role of MRI in lymphedema diagnosis and management. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 5.

Dou, Qianhui, Aaron K Grant, Cody Callahan, Patricia Coutinho de Souza, David Mwin, Adam L Booth, Imad Nasser, Marwan Moussa, Muneeb Ahmed, and Leo L Tsai. (2023) 2023. “PFKFB3-Mediated Pro-Glycolytic Shift in Hepatocellular Carcinoma Proliferation.”. Cellular and Molecular Gastroenterology and Hepatology 15 (1): 61-75. https://doi.org/10.1016/j.jcmgh.2022.09.009.

BACKGROUND & AIMS: Metabolic reprogramming, in particular, glycolytic regulation, supports abnormal survival and growth of hepatocellular carcinoma (HCC) and could serve as a therapeutic target. In this study, we sought to identify glycolytic regulators in HCC that could be inhibited to prevent tumor progression and could also be monitored in vivo, with the goal of providing a theragnostic alternative to existing therapies.

METHODS: An orthotopic HCC rat model was used. Tumors were stimulated into a high-proliferation state by use of off-target liver ablation and were compared with lower-proliferating controls. We measured in vivo metabolic alteration in tumors before and after stimulation, and between stimulated tumors and control tumors using hyperpolarized 13C magnetic resonance imaging (MRI) (h13C MRI). We compared metabolic alterations detected by h13C MRI to metabolite levels from ex vivo mass spectrometry, mRNA levels of key glycolytic regulators, and histopathology.

RESULTS: Glycolytic lactate flux increased within HCC tumors 3 days after tumor stimulation, correlating positively with tumor proliferation as measured with Ki67. This was associated with a shift towards aerobic glycolysis and downregulation of the pentose phosphate pathway detected by mass spectrometry. MRI-measured lactate flux was most closely coupled with PFKFB3 expression and was suppressed with direct inhibition using PFK15.

CONCLUSIONS: Inhibition of PFKFB3 prevents glycolytic-mediated HCC proliferation, trackable by in vivo h13C MRI.

Lee, Kyuwon, Brian Ellison, Magdy Selim, Ngo H Long, Aristotelis Filippidis, Ajith J Thomas, Pascal Spincemaille, Yi Wang, and Salil Soman. (2023) 2023. “Quantitative Susceptibility Mapping Improves Cerebral Microbleed Detection Relative to Susceptibility-Weighted Images.”. Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging 33 (1): 138-46. https://doi.org/10.1111/jon.13054.

BACKGROUND AND PURPOSE: Cerebral microbleed (CMB) detection impacts disease diagnosis and management. Susceptibility-weighted imaging (SWI) MRI depictions of CMBs are used with phase images (SWIP) to distinguish blood from calcification, via qualitative intensity evaluation (bright/dark). However, the intensities depicted for a single lesion can vary within and across consecutive SWIP image planes, impairing the classification of findings as a CMB. We hypothesize that quantitative susceptibility mapping (QSM) MRI, which maps tissue susceptibility, demonstrates less in- and through-plane intensity variation, improving the clinician's ability to categorize a finding as a CMB.

METHODS: Forty-eight patients with acute intracranial hemorrhage who received multi-echo gradient echo MRI used to generate both SWI/SWIP and morphology-enabled dipole inversion QSM images were enrolled. Five hundred and sixty lesions were visually classified as having homogeneous or heterogeneous in-plane and through-plane intensity by a neuroradiologist and two diagnostic radiology residents using published rating criteria. When available, brain CT scans were analyzed for calcification or acute hemorrhage. Relative risk (RR) ratios and confidence intervals (CIs) were calculated using a generalized linear model with log link and binary error.

RESULTS: QSM showed unambiguous lesion signal intensity three times more frequently than SWIP (RR = 0.3235, 95% CI 0.2386-0.4386, p<.0001). The probability of QSM depicting homogeneous lesion intensity was three times greater than SWIP for small (RR = 0.3172, 95% CI 0.2382-0.4225, p<.0001), large (RR = 0.3431, 95% CI 0.2045-0.5758, p<.0001), lobar (RR = 0.3215, 95% CI 0.2151-0.4805, p<.0001), cerebellar (RR = 0.3215, 95% CI 0.2151-0.4805, p<.0001), brainstem (RR = 0.3100, 95% CI 0.1192-0.8061, p = .0163), and basal ganglia (RR = 0.3380, 95% CI 0.1980-0.5769, p<.0001) lesions.

CONCLUSIONS: QSM more consistently demonstrates interpretable lesion intensity compared to SWIP as used for distinguishing CMBs from calcification.

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.

Kim, Geunwon, Michael Adondakis, Martin P Smith, Dhruv Singhal, and Leo L Tsai. (2023) 2023. “Rate of Incidental Edema in the Contralateral Arm of Patients With Unilateral Postsurgical Secondary Upper Extremity Lymphedema.”. Lymphatic Research and Biology 21 (2): 111-17. https://doi.org/10.1089/lrb.2021.0022.

Background: Secondary upper extremity lymphedema occurs after an insult such as surgery. One theory suggests underlying lymphatic dysfunction predisposing certain patients into developing secondary lymphedema. We aim to determine the rate of incidental edema in the contralateral upper extremity of patients with secondary unilateral lymphedema. Methods and Results: MRI of the upper extremities were obtained in patients with lymphedema who were referred by a lymphedema clinic from 2017 to 2019. Axial short-tau inversion recovery MR images of the symptomatic and contralateral arms were retrospectively reviewed and edema severity was graded. Interobserver agreement was calculated. Indocyanine green (ICG) lymphography was compared against MRI stage in symptomatic and contralateral. Age, symptom duration, body mass index (BMI), and history of chemotherapy were compared between patients with and without contralateral limb lymphedema. ICG severity was compared against MRI stage. Seventy-eight patients were analyzed. The MRI stages of symptomatic versus contralateral arms were 1.7 ± 1.1 versus 0.1 ± 0.4 (p < 0.00001). Interobserver agreement was 0.86 (0.79-0.94). Of the patients with MRI Stage 1 or above in the symptomatic arm (n = 64), 55 (82.1%) patients demonstrated no abnormality in the contralateral arm. Nine patients (14.1%) demonstrated asymptomatic edema (MRI Stage 1). The mean ICG lymphography stage of symptomatic versus contralateral arms was 1.83 ± 0.96 versus 0.04 ± 0.25 (p < 0.00001). There was no difference in the age, symptom duration, BMI, or history of chemotherapy between patients with or without edema in the contralateral arm. Conclusion: Asymptomatic contralateral edema was detected in 14.1% of patients with unilateral secondary upper extremity lymphedema using MRI modality.

Alsop, David C, Ece Ercan, Olivier M Girard, Alex L Mackay, Carl A Michal, Gopal Varma, Elena Vinogradov, and Guillaume Duhamel. (2023) 2023. “Inhomogeneous Magnetization Transfer Imaging: Concepts and Directions for Further Development.”. NMR in Biomedicine 36 (6): e4808. https://doi.org/10.1002/nbm.4808.

Off-resonance radio frequency irradiation can induce the ordering of proton spins in the dipolar fields of their neighbors, in molecules with restricted mobility. This dipolar order decays with a characteristic relaxation time, T1D , that is very different from the T1 and T2 relaxation of the nuclear alignment with the main magnetic field. Inhomogeneous magnetization transfer (ihMT) imaging is a refinement of magnetization transfer (MT) imaging that isolates the MT signal dependence on dipolar order relaxation times within motion-constrained molecules. Because T1D relaxation is a unique contrast mechanism, ihMT may enable improved characterization of tissue. Initial work has stressed the high correlation between ihMT signal and myelin density. Dipolar order relaxation appears to be much longer in membrane lipids than other molecules. Recent work has shown, however, that ihMT acquisitions may also be adjusted to emphasize different ranges of T1D . These newer approaches may be sensitive to other microstructural components of tissue. Here, we review the concepts and history of ihMT and outline the requirements for further development to realize its full potential.