All Publications

  • Smaller Diameter and Adjustable Diameter Transjugular Intrahepatic Portosystemic Shunts. Seminars in interventional radiology Gupta, A. N., Sze, D. Y., Rigas, D. A. 2023; 40 (1): 21-26

    Abstract

    Complications of overshunting, including hepatic encephalopathy and hepatic insufficiency, remain prevalent following transjugular intrahepatic portosystemic shunt (TIPS) creation. Smaller diameter TIPS may reduce the risk of overshunting, but the use of smaller stents must be weighed against the risk of undershunting and persistent or recurrent hemorrhage, ascites, and other complications of portal hypertension. This article explores the question of optimal shunt diameter by examining outcomes for smaller diameter TIPS stent-grafts (<10 mm), underdilated stent-grafts, and variable diameter stent-grafts.

    View details for DOI 10.1055/s-0043-1764285

    View details for PubMedID 37152799

    View details for PubMedCentralID PMC10159728

  • Yttrium-90 Radioembolization of Unresectable Intrahepatic Cholangiocarcinoma: Long-Term Follow-up for a 136-Patient Cohort. Cardiovascular and interventional radiology Gupta, A. N., Gordon, A. C., Gabr, A., Kalyan, A., Kircher, S. M., Mahalingam, D., Mulcahy, M. F., Merkow, R. P., Yang, A. D., Bentrem, D. J., Caicedo-Ramirez, J. C., Riaz, A., Thornburg, B., Desai, K., Sato, K. T., Hohlastos, E. S., Kulik, L., Benson, A. B., Salem, R., Lewandowski, R. J. 2022

    Abstract

    PURPOSE: Unresectable intrahepatic cholangiocarcinoma (ICC) signifies a poor prognosis with limited treatment options beyond systemic chemotherapy. This study's purpose was to evaluate the safety, efficacy, and potential for downstaging to resection of yttrium-90 (Y90) radioembolization for treatment of unresectable ICC.MATERIALS AND METHODS: From 2004 to 2020, 136 patients with unresectable ICC were treated with radioembolization at a single institution. Retrospective review was performed of a prospectively collected database. Outcomes were (1) biochemical and clinical toxicities, (2) local tumor response, (3) time to progression, and (4) overall survival (OS) after Y90. Univariate/multivariate survival analyses were performed. A subgroup analysis was performed to calculate post-resection recurrence and OS in patients downstaged to resection after Y90.RESULTS: Grade 3+clinical and biochemical toxicities were 7.6% (n=10) and 4.9% (n=6), respectively. Best index lesion response was complete response in 2 (1.5%), partial response in 42 (32.1%), stable disease in 82 (62.6%), and progressive disease in 5 (3.8%) patients. Median OS was 14.2months. Solitary tumor (P<0.001), absence of vascular involvement (P=0.009), and higher serum albumin (P<0.001) were independently associated with improved OS. Eleven patients (8.1%) were downstaged to resection and 2 patients (1.5%) were bridged to transplant. R0-resection was achieved in 8/11 (72.7%). Post-resection median recurrence and OS were 26.3months and 39.9months, respectively.CONCLUSION: Y90 has an acceptable safety profile and high local disease control rates for the treatment of unresectable ICC. Downstaging to resection with>3years survival supports the therapeutic role of Y90 for unresectable ICC.LEVEL OF EVIDENCE: Level 3, single-arm single-center cohort study.

    View details for DOI 10.1007/s00270-022-03183-2

    View details for PubMedID 35732931

  • Direct mitral regurgitation quantification in hypertrophic cardiomyopathy using 4D flow CMR jet tracking: evaluation in comparison to conventional CMR JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE Gupta, A. N., Avery, R., Soulat, G., Allen, B. D., Collins, J. D., Choudhury, L., Bonow, R. O., Carr, J., Markl, M., Elbaz, M. M. 2021; 23 (1): 138

    Abstract

    Quantitative evaluation of mitral regurgitation (MR) in hypertrophic cardiomyopathy (HCM) by cardiovascular magnetic resonance (CMR) relies on an indirect volumetric calculation. The aim of this study was to directly assess and quantify MR jets in patients with HCM using 4D flow CMR jet tracking in comparison to standard-of-care CMR indirect volumetric method.This retrospective study included patients with HCM undergoing 4D flow CMR. By the indirect volumetric method from CMR, MR volume was quantified as left ventricular stroke volume minus forward aortic volume. By 4D flow CMR direct jet tracking, multiplanar reformatted planes were positioned in the peak velocity of the MR jet during systole to calculate through-plane regurgitant flow. MR severity was collected for agreement analysis from a clinical echocardiograms performed within 1 month of CMR. Inter-method and inter-observer agreement were assessed by intraclass correlation coefficient (ICC), Bland-Altman analysis, and Cohen's kappa.Thirty-seven patients with HCM were included. Direct jet tracking demonstrated good inter-method agreement of MR volume compared to the indirect volumetric method (ICC = 0.80, p = 0.004) and fair agreement of MR severity (kappa = 0.27, p = 0.03). Direct jet tracking showed higher agreement with echocardiography (kappa = 0.35, p = 0.04) than indirect volumetric method (kappa = 0.16, p = 0.35). Inter-observer reproducibility of indirect volumetric method components revealed the lowest reproducibility in end-systolic volume (ICC = 0.69, p = 0.15). Indirect volumetric method showed good agreement of MR volume (ICC = 0.80, p = 0.003) and fair agreement of MR severity (kappa = 0.38, p < 0.001). Direct jet tracking demonstrated (1) excellent inter-observer reproducibility of MR volume (ICC = 0.97, p < 0.001) and MR severity (kappa = 0.84, p < 0.001) and (2) excellent intra-observer reproducibility of MR volume (ICC = 0.98, p < 0.001) and MR severity (kappa = 0.88, p < 0.001).Quantifying MR and assessing MR severity by indirect volumetric method in HCM patients has limited inter-observer reproducibility. 4D flow CMR jet tracking is a potential alternative technique to directly quantify and assess MR severity with excellent inter- and intra-observer reproducibility and higher agreement with echocardiography in this population.

    View details for DOI 10.1186/s12968-021-00828-y

    View details for Web of Science ID 000727720800001

    View details for PubMedID 34865629

    View details for PubMedCentralID PMC8647422

  • Valvular regurgitation flow jet assessment using in vitro 4D flow MRI: Implication for mitral regurgitation MAGNETIC RESONANCE IN MEDICINE Lee, J., Gupta, A. N., Ma, L. E., Scott, M. B., Mason, O. R., Wu, E., Thomas, J. D., Markl, M. 2022; 87 (4): 1923-1937

    Abstract

    The purpose of this study was to evaluate the accuracy of four-dimensional (4D) flow MRI for direct assessment of peak velocity, flow volume, and momentum of a mitral regurgitation (MR) flow jets using an in vitro pulsatile jet flow phantom. We systematically investigated the impact of spatial resolution and quantification location along the jet on flow quantities with Doppler ultrasound as a reference for peak velocity.Four-dimensional flow MRI data of a pulsatile jet through a circular, elliptical, and 3D-printed patient-specific MR orifice model was acquired with varying spatial resolution (1.5-5 mm isotropic voxel). Flow rate and momentum of the jet were quantified at various axial distances (x = 0-50 mm) and integrated over time to calculate Voljet and MTIjet . In vivo assessment of Voljet and MTIjet was performed on 3 MR patients.Peak velocities were comparable to Doppler ultrasound (3% error, 1.5 mm voxel), but underestimated with decreasing spatial resolution (-40% error, 5 mm voxel). Voljet was similar to regurgitant volume (RVol) within 5 mm, and then increased linearly with the axial distance (19%/cm) because of flow entrainment. MTIjet remained steady throughout the jet (2%/cm) as theoretically predicted. Four and 9 voxels across the jet were required to measure flow volume and momentum-time-integral within 10% error, respectively.Four-dimensional flow MRI detected accurate peak velocity, flow rate, and momentum for in vitro MR-mimicking flow jets. Spatial resolution significantly impacted flow quantitation, which otherwise followed predictions of flow entrainment and momentum conservation. This study provides important preliminary information for accurate in vivo MR assessment using 4D flow MRI.

    View details for DOI 10.1002/mrm.29082

    View details for Web of Science ID 000718874400001

    View details for PubMedID 34783383

  • 4D flow MRI left atrial kinetic energy in hypertrophic cardiomyopathy is associated with mitral regurgitation and left ventricular outflow tract obstruction INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING Gupta, A. N., Soulat, G., Avery, R., Allen, B. D., Collins, J. D., Choudhury, L., Bonow, R. O., Carr, J., Markl, M., Elbaz, M. M. 2021; 37 (9): 2755-2765

    Abstract

    To noninvasively assess left atrial (LA) kinetic energy (KE) in hypertrophic cardiomyopathy (HCM) patients using 4D flow MRI and evaluate coupling associations with mitral regurgitation (MR) and left ventricular outflow tract (LVOT) obstruction. Twenty-nine retrospectively identified patients with HCM underwent 4D flow MRI. MRI-estimated peak LVOT pressure gradient (∆PMRI) was used to classify patients into non-obstructive and obstructive HCM. Time-resolved volumetric LA kinetic energy (KELA) was computed throughout systole. Average systolic (KELA-avg) and peak systolic (KELA-peak) KELA were compared between non-obstructive and obstructive HCM groups, and associations to MR severity and LVOT ∆PMRI were tested.The study included 15 patients with non-obstructive HCM (58.6 [45.9, 65.2] years, 7 females) and 14 patients with obstructive HCM (51.9 [47.6, 62.6] years, 6 females). Obstructive HCM patients demonstrated significantly elevated instantaneous KELA over all systolic time-points compared to non-obstructive HCM (P < 0.05). Obstructive HCM patients also demonstrated higher KELA-avg (14.8 [10.6, 20.4] J/m3 vs. 33.4 [23.9, 61.3] J/m3, P < 0.001) and KELA-peak (22.1 [15.9, 28.7] J/m3 vs. 57.2 [44.5, 121.4] J/m3, P < 0.001) than non-obstructive HCM. MR severity was significantly correlated with KELA-avg (rho = 0.81, P < 0.001) and KELA-peak (rho = 0.79, P < 0.001). LVOT ∆PMRI was strongly correlated with KELA metrics in obstructive HCM (KELA-avg: rho = 0.86, P < 0.001; KELA-peak: rho = 0.85, P < 0.001).In HCM patients, left atrial kinetic energy, by 4D flow MRI, is associated with MR severity and the degree of LVOT obstruction.

    View details for DOI 10.1007/s10554-021-02167-6

    View details for Web of Science ID 000613638900001

    View details for PubMedID 33523363

  • Safety and Efficacy of Segmental Yttrium-90 Radioembolization for Hepatocellular Carcinoma after Transjugular Intrahepatic Portosystemic Shunt Creation JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Gordon, A. C., Gupta, A. N., Gabr, A., Thornburg, B. G., Kulik, L. M., Ganger, D. R., Maddur, H., Flamm, S. L., Boike, J. R., Moore, C. M., Borja-Cacho, D., Christopher, D. A., Katariya, N. N., Ladner, D. P., Caicedo-Ramirez, J. C., Riaz, A., Salem, R., Lewandowski, R. J. 2021; 32 (2): 211-219

    Abstract

    To evaluate safety and efficacy of segmental yttrium-90 (Y90) radioembolization for hepatocellular carcinoma (HCC) after transjugular intrahepatic portosystemic shunt (TIPS) placement. The hypothesis was liver sparing segmental Y90 for HCC after TIPS would provide high antitumor response with a tolerable safety profile.This single-arm retrospective study included 39 patients (16 women, 23 men) with ages 49-81 years old who were treated with Y90. Child-Pugh A/B liver dysfunction was present in 72% (28/39) with a median Model for End-stage Liver Disease score of 18 (95% confidence interval, 16.4-19.4). Primary outcomes were clinical and biochemical toxicities and antitumor imaging response by World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. Secondary outcomes were orthotopic liver transplantation (OLT), time to progression (TTP), and overall survival (OS) estimates by the Kaplan-Meier method.The 30-day mortality was 0%. Grade 3+ clinical adverse events and grade 3+ hyperbilirubinemia occurred in 5% (2/39) and 0% (0/39), respectively. Imaging response was achieved in 58% (22/38, WHO criteria) and 74% (28/38, EASL criteria), respectively. Median TTP was 16.1 months for any cause and 27.5 months for primary index lesions. OLT was completed in 88% (21/24) of listed patients at a median time of 6.1 months (range, 0.9-11.7 months). Median OS was 31.6 months and 62.9 months censored and uncensored to OLT, respectively.Segmental Y90 for HCC appears safe and efficacious in patients after TIPS. Preserved transplant eligibility suggests that Y90 is a useful tool for bridging these patients to liver transplantation.

    View details for DOI 10.1016/j.jvir.2020.09.007

    View details for Web of Science ID 000691617400009

    View details for PubMedID 33349507

  • Intracardiac and Vascular Hemodynamics with Cardiovascular Magnetic Resonance in Heart Failure HEART FAILURE CLINICS Gupta, A. N., Markl, M., Elbaz, M. M. 2021; 17 (1): 135-147

    Abstract

    In heart failure (HF), the impaired heart loses its ability to competently eject blood during systole or fill with blood during diastole, manifesting in multifaceted abnormal intracardiac or intravascular flow dynamics. Conventional imaging techniques are limited in their ability to evaluate multidirectional multidimensional flow alterations in HF. Four-dimensional (4-D) flow magnetic resonance imaging (MRI) has emerged as a promising technique to comprehensively visualize and quantify changes in 3-dimensional blood flow dynamics in complex cardiovascular diseases. This article reviews emerging applications of 4-D flow MRI hemodynamic markers in HF and etiologies at risk of progressing to HF.

    View details for DOI 10.1016/j.hfc.2020.08.010

    View details for Web of Science ID 000591792600012

    View details for PubMedID 33220882

  • Complicated Double-Orifice Mitral Regurgitation: Combined Hemodynamic Assessment Using Echocardiography and Four-Dimensional Flow Magnetic Resonance Imaging. CASE (Philadelphia, Pa.) Lee, J., El Hangouche, N., Gupta, A. N., Markl, M., Kim, S., Wilcox, J., Thomas, J. D. 2020; 4 (6): 494-499

    View details for DOI 10.1016/j.case.2020.08.001

    View details for PubMedID 33376841

    View details for PubMedCentralID PMC7756160

  • Multimodal imaging of a giant left ventricular basal aneurysm and resulting intracardiac flow disturbances EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING Gupta, A., Soulat, G., Markl, M., Thomas, J., Avery, R. 2020; 21 (9): 1050

    View details for DOI 10.1093/ehjci/jeaa080

    View details for Web of Science ID 000566727900023

    View details for PubMedID 32361763

  • Activity Recognition in Individuals Walking With Assistive Devices: The Benefits of Device-Specific Models. JMIR rehabilitation and assistive technologies Lonini, L., Gupta, A., Deems-Dluhy, S., Hoppe-Ludwig, S., Kording, K., Jayaraman, A. 2017; 4 (2): e8

    Abstract

    Wearable sensors gather data that machine-learning models can convert into an identification of physical activities, a clinically relevant outcome measure. However, when individuals with disabilities upgrade to a new walking assistive device, their gait patterns can change, which could affect the accuracy of activity recognition.The objective of this study was to assess whether we need to train an activity recognition model with labeled data from activities performed with the new assistive device, rather than data from the original device or from healthy individuals.Data were collected from 11 healthy controls as well as from 11 age-matched individuals with disabilities who used a standard stance control knee-ankle-foot orthosis (KAFO), and then a computer-controlled adaptive KAFO (Ottobock C-Brace). All subjects performed a structured set of functional activities while wearing an accelerometer on their waist, and random forest classifiers were used as activity classification models. We examined both global models, which are trained on other subjects (healthy or disabled individuals), and personal models, which are trained and tested on the same subject.Median accuracies of global and personal models trained with data from the new KAFO were significantly higher (61% and 76%, respectively) than those of models that use data from the original KAFO (55% and 66%, respectively) (Wilcoxon signed-rank test, P=.006 and P=.01). These models also massively outperformed a global model trained on healthy subjects, which only achieved a median accuracy of 53%. Device-specific models conferred a major advantage for activity recognition.Our results suggest that when patients use a new assistive device, labeled data from activities performed with the specific device are needed for maximal precision activity recognition. Personal device-specific models yield the highest accuracy in such scenarios, whereas models trained on healthy individuals perform poorly and should not be used in patient populations.

    View details for DOI 10.2196/rehab.7317

    View details for PubMedID 28798008

    View details for PubMedCentralID PMC5571233

  • Activity Recognition in Patients with Lower Limb Impairments: Do we need training data from each patient? Lonini, L., Gupta, A., Kording, K., Jayaraman, A., Patton, J., Barbieri, R., Ji, J., Jabbari, E., Dokos, S., Mukkamala, R., Guiraud, D., Jovanov, E., Dhaher, Y., Panescu, D., Vangils, M., Wheeler, B., Dhawan, A. P. IEEE. 2016: 3265-3268

    Abstract

    Machine learning allows detecting specific physical activities using data from wearable sensors. Such a quantification of patient mobility over time promises to accurately inform clinical decisions for physical rehabilitation. There are two strategies of setting up the machine learning problem: detect one patient's activities using data from the same patient (personal model) or detect their activities using data from other patients (global model), and we currently do not know if personal models are necessary. Here we consider the problem of detecting physical activities from a waist-worn accelerometer in patients who use a knee-ankle-foot orthosis (KAFO) to walk. We show that while a model based on healthy subjects has low accuracy, the global model performs as well as the personal model. This is encouraging because it suggests that condition-specific activity recognition algorithms are sufficient and that no data from individual patients is necessary.

    View details for Web of Science ID 000399823503154

    View details for PubMedID 28269004

  • Prediction and validation of enzyme and transporter off-targets for metformin JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS Yee, S., Lin, L., Merski, M., Keiser, M. J., Gupta, A., Zhang, Y., Chien, H., Shoichet, B. K., Giacomini, K. M. 2015; 42 (5): 463-475

    Abstract

    Metformin, an established first-line treatment for patients with type 2 diabetes, has been associated with gastrointestinal (GI) adverse effects that limit its use. Histamine and serotonin have potent effects on the GI tract. The effects of metformin on histamine and serotonin uptake were evaluated in cell lines overexpressing several amine transporters (OCT1, OCT3 and SERT). Metformin inhibited histamine and serotonin uptake by OCT1, OCT3 and SERT in a dose-dependent manner, with OCT1-mediated amine uptake being most potently inhibited (IC50 = 1.5 mM). A chemoinformatics-based method known as Similarity Ensemble Approach predicted diamine oxidase (DAO) as an additional intestinal target of metformin, with an E-value of 7.4 × 10(-5). Inhibition of DAO was experimentally validated using a spectrophotometric assay with putrescine as the substrate. The Ki of metformin for DAO was measured to be 8.6 ± 3.1 mM. In this study, we found that metformin inhibited intestinal amine transporters and DAO at concentrations that may be achieved in the intestine after therapeutic doses. Further studies are warranted to determine the relevance of these interactions to the adverse effects of metformin on the gastrointestinal tract.

    View details for DOI 10.1007/s10928-015-9436-y

    View details for Web of Science ID 000361883600004

    View details for PubMedID 26335661

    View details for PubMedCentralID PMC4656030