Clifford R Weiss

Johns Hopkins University, Baltimore, Maryland, United States

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Publications (38)93.18 Total impact

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    ABSTRACT: Purpose To assess intrapericardial delivery of microencapsulated, xenogeneic human mesenchymal stem cells (hMSCs) by using x-ray fused with magnetic resonance (MR) imaging (x-ray/MR imaging) guidance as a potential treatment for ischemic cardiovascular disease in an immunocompetent swine model. Materials and Methods All animal experiments were approved by the institutional animal care and use committee. Stem cell microencapsulation was performed by using a modified alginate-poly-l-lysine-alginate encapsulation method to include 10% (wt/vol) barium sulfate to create barium-alginate microcapsules (BaCaps) that contained hMSCs. With x-ray/MR imaging guidance, eight female pigs (approximately 25 kg) were randomized to receive either BaCaps with hMSCs, empty BaCaps, naked hMSCs, or saline by using a percutaneous subxiphoid approach and were compared with animals that received empty BaCaps (n = 1) or BaCaps with hMSCs (n = 2) by using standard fluoroscopic delivery only. MR images and C-arm computed tomographic (CT) images were acquired before injection and 1 week after delivery. Animals were sacrificed immediately or at 1 week for histopathologic validation. Cardiac function between baseline and 1 week after delivery was evaluated by using a paired Student t test. Results hMSCs remained highly viable (94.8% ± 6) 2 days after encapsulation in vitro. With x-ray/MR imaging, successful intrapericardial access and delivery were achieved in all animals. BaCaps were visible fluoroscopically and at C-arm CT immediately and 1 week after delivery. Whereas BaCaps were free floating immediately after delivery, they consolidated into a pseudoepicardial tissue patch at 1 week, with hMSCs remaining highly viable within BaCaps; naked hMSCs were poorly retained. Follow-up imaging 1 week after x-ray/MR imaging-guided intrapericardial delivery showed no evidence of pericardial adhesion and/or effusion or adverse effect on cardiac function. In contradistinction, BaCaps delivery with x-ray fluoroscopy without x-ray/MR imaging (n = 3) resulted in pericardial adhesions and poor hMSC viability after 1 week. Conclusion Intrapericardial delivery of BaCaps with hMSCs leads to high cell retention and survival. With x-ray/MR imaging guidance, intrapericardial delivery can be performed safely in the absence of preexisting pericardial effusion to provide a novel route for cardiac cellular regenerative therapy. © RSNA, 2014 Online supplemental material is available for this article.
    Radiology 04/2014; · 6.34 Impact Factor
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    ABSTRACT: Cholangiocarcinoma (CCA) presents significant diagnostic challenges, resulting in late patient diagnosis and poor survival rates. Primary Sclerosing Cholangitis (PSC) patients pose a particularly difficult clinical dilemma, since they harbor chronic biliary strictures that are difficult to distinguish from CCA. MicroRNAs (miRs) have recently emerged as a valuable class of diagnostic markers; however, thus far, neither extracellular vesicles (EVs) nor miRs within EVs have been investigated in human bile. We aimed to comprehensively characterize human biliary EVs, including their miR content. Conclusion: We have established the presence of extracellular vesicles in human bile. In addition, we have demonstrated that human biliary EVs contain abundant miR species, which are stable and therefore amenable to the development of disease marker panels. Furthermore, we have characterized the protein content, size, numbers and size distribution of human biliary EVs. Utilizing Multivariate Organization of Combinatorial Alterations (MOCA), we defined a novel biliary vesicle miR-based panel for CCA diagnosis which demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 patients with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 patients with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR-based disease markers in bile. Finally, we report the development of a novel bile-based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility. (Hepatology 2014;).
    Hepatology 02/2014; · 12.00 Impact Factor
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    ABSTRACT: To evaluate the histopathologic sequelae of bariatric embolization on the gastric mucosa and to correlate with immunohistochemical evaluation of the gastric fundus, antrum, and duodenum. This study was performed on 12 swine stomach and duodenum specimens after necropsy. Of the 12 swine, 6 had previously undergone bariatric embolization of the gastric fundus, and the 6 control swine had undergone a sham procedure with saline. Gross pathologic, histopathologic, and immunohistochemical examinations of the stomach and duodenum were performed. Specifically, mucosal integrity, fibrosis, ghrelin-expressing cells, and gastrin-expressing cells were assessed. Gross and histopathologic evaluation of treatment animals showed healing or healed mucosal ulcers in 50% of animals, with gastritis in 100% of treatment animals and in five of six control animals. The ghrelin-immunoreactive mean cell density was significantly lower in the gastric fundus in the treated animals compared with control animals (15.3 vs 22.0, P < .01) but similar in the gastric antrum (9.3 vs 14.3, P = .08) and duodenum (8.5 vs 8.6, P = .89). The gastrin-expressing cell density was significantly lower in the antrum of treated animals compared with control animals (82.2 vs 126.4, P = .03). A trend toward increased fibrosis was suggested in the gastric fundus of treated animals compared with controls (P = .07). Bariatric embolization resulted in a significant reduction in ghrelin-expressing cells in the gastric fundus without evidence of upregulation of ghrelin-expressing cells in the duodenum. Healing ulcerations in half of treated animals underscores the need for additional refinement of this procedure.
    Journal of vascular and interventional radiology: JVIR 01/2014; · 1.81 Impact Factor
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    ABSTRACT: Major depressive disorder (MDD) is associated with an increased risk for developing coronary artery disease (CAD). Recently, pericardial adipose tissue, a metabolically active visceral fat depot surrounding the heart, has been implicated in the pathogenesis of CAD. Therefore, we investigated pericardial adipose tissue volumes in patients with MDD and compared them to healthy comparison subjects. In this case-control study at a university medical center, 50 male and female in-patients with MDD and 25 healthy men and women were examined. The main outcome measures were the volumes of pericardial adipose tissue, intra-abdominal adipose tissue (IaAT) and subcutaneous adipose tissue (ScAT) which were measured using magnetic resonance imaging. The pericardial adipose tissue volumes were greater in men and women with MDD compared with the healthy comparison group following adjustments for the effects of age, weight, height, and physical activity. This study expands our knowledge about the alterations in body composition that occur in patients with MDD. The findings are highly relevant for understanding the comorbidity between heart disease and depressive disorders.
    Acta Psychiatrica Scandinavica 01/2014; · 4.86 Impact Factor
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    ABSTRACT: Image-guided treatment of low-flow vascular (venous or lymphatic) malformations presents a challenging visualization problem, regardless of the imaging modality being used for guidance. The purpose of this study was to employ a new magnetic resonance imaging (MRI) sequence, T2 -weighted interrupted balanced steady-state free precession (T2 W-iSSFP), for real-time image guidance of needle insertion. T2 W-iSSFP uses variable flip angle balanced steady-state free precession (bSSFP, a.k.a. SSFP) to establish T2 -weighting and fat suppression. Swine (n = 3) and patients (n = 4, three female, all with venous malformations) were enrolled in the assessment. T2 -weighted turbo spin echo (T2 -TSE) with spectral adiabatic inversion recovery (SPAIR), SPAIR-T2 -TSE or T2 -TSE for short, was used as the reference. T2 -weighted half Fourier acquired single shot turbo spin echo (T2 -HASTE) with SPAIR (SPAIR-T2 -HASTE, T2 -HASTE for short), fat saturated bSSFP (FS-SSFP), and T2 W-iSSFP were imaged. Numeric metrics, namely, contrast-to-noise ratio (CNR) efficiency (CNR divided by the square root of acquisition time) and local sharpness (the reciprocal of edge width), were used to assess image quality. MR-guided sclerotherapy was performed on the same patients using real-time T2 W-iSSFP to guide needle insertion. Comparing the visualization of needles in the images of swine, the local sharpness (mm(-1) ) was: 0.21 ± 0.06 (T2 -HASTE), 0.48 ± 0.02 (FS-SSFP), and 0.49 ± 0.03 (T2 W-iSSFP). T2 W-iSSFP is higher than T2 -HASTE (P < 0.001). For the patient images, their CNR efficiencies were: 797 ± 66 (T2 -HASTE), 281 ± 44 (FS-SSFP), and 860 ± 29 (T2 W-iSSFP). T2 W-iSSFP is higher than FS-SSFP (P < 0.02). The frame rate of T2 W-iSSFP was 2.5-3.5 frames per second. All MR-guided sclerotherapy procedures were successful, with all needles (six punctures) placed in the targets. T2 W-iSSFP provides effective lesion identification and needle visualization. This new pulse sequence can be used for MR-guided sclerotherapy of low-flow vascular malformations. It may have potential use in other MR-guided procedures where heavily T2 -weighted real-time images are needed.J. Magn. Reson. Imaging 2014. © 2014 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 01/2014; · 2.57 Impact Factor
  • Journal of Vascular and Interventional Radiology. 01/2014; 25(4):661–662.
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    ABSTRACT: PURPOSE: To develop and evaluate software-based methods for improving the workflow of magnetic resonance (MR)-guided percutaneous interventions. MATERIALS AND METHODS: A set of methods was developed that allows the user to: 1) plan an entire procedure, 2) directly apply this plan to skin entry site localization without further imaging, and 3) place a needle under real-time MR guidance with automatic alignment of three orthogonal slices along a planned trajectory with preference to the principal patient axes. To validate targeting accuracy and time, phantom experiments (96 targets) and in vivo paraspinal and kidney needle punctures in two pigs (55 targets) were performed. The influence of trajectory obliquity, level of experience, and organ motion on targeting accuracy and time was analyzed. RESULTS: Mean targeting error was 1.8 ± 0.9 mm (in vitro) and 2.9 ± 1.0 mm (in vivo) in all directions. No statistically significant differences in targeting accuracy between single- and double-oblique trajectories, novice and expert users, or paraspinal and kidney punctures were observed. The average time (in vivo) from trajectory planning to verification of accurate needle placement was 6 minutes. CONCLUSION: The developed methods allow for accurate needle placement along complex trajectories and are anticipated to reduce table time for MR-guided percutaneous needle interventions. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.
    Journal of Magnetic Resonance Imaging 01/2013; · 2.57 Impact Factor
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    ABSTRACT: Microencapsulation of therapeutic cells has been widely pursued to achieve cellular immunoprotection following transplantation. Initial clinical studies have shown the potential of microencapsulation using semi-permeable alginate layers, but much needs to be learned about the optimal delivery route, in vivo pattern of engraftment, and microcapsule stability over time. In parallel with noninvasive imaging techniques for 'naked' (i.e. unencapsulated) cell tracking, microcapsules have now been endowed with contrast agents that can be visualized by (1) H MRI, (19) F MRI, X-ray/computed tomography and ultrasound imaging. By placing the contrast agent formulation in the extracellular space of the hydrogel, large amounts of contrast agents can be incorporated with negligible toxicity. This has led to a new generation of imaging biomaterials that can render cells visible with multiple imaging modalities. Copyright © 2012 John Wiley & Sons, Ltd.
    NMR in Biomedicine 12/2012; · 3.45 Impact Factor
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    ABSTRACT: OBJECTIVE: The study was designed to determine the distance between the visible "ice-ball" and the lethal temperature isotherm for normal renal tissue during cryoablation. METHODS: The Animal Care Committee approved the study. Nine adult swine were used: three to determine the optimum tissue stain and six to test the hypotheses. They were anesthetized and the left renal artery was catheterized under fluoroscopy. Under MR guidance, the kidney was ablated and (at end of a complete ablation) the nonfrozen renal tissue (surrounding the "ice-ball") was stained via renal artery catheter. Kidneys were explanted and sent for slide preparation and examination. From each slide, we measured the maximum, minimum, and an in-between distance from the stained to the lethal tissue boundaries (margin). We examined each slide for evidence of "heat pump" effect. RESULTS: A total of 126 measurements of the margin (visible "ice-ball"-lethal margin) were made. These measurements were obtained from 29 slides prepared from the 6 test animals. Mean width was 0.75 ± 0.44 mm (maximum 1.15 ± 0.51 mm). It was found to increase adjacent to large blood vessels. No "heat pump" effect was noted within the lethal zone. Data are limited to normal swine renal tissue. CONCLUSIONS: Considering the effects of the "heat pump" phenomenon for normal renal tissue, the margin was measured to be 1.15 ± 0.51 mm. To approximate the efficacy of the "gold standard" (partial nephrectomy, ~98 %), a minimum margin of 3 mm is recommended (3 × SD). Given these assumptions and extrapolating for renal cancer, which reportedly is more cryoresistant with a lethal temperature of -40 °C, the recommended margin is 6 mm.
    CardioVascular and Interventional Radiology 08/2012; · 2.09 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 02/2012; 14 Suppl 1:P63. · 4.44 Impact Factor
  • Clifford R. Weiss
    Critical Reviews in Computed Tomography. 12/2011; 45(5-6).
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    ABSTRACT: The susceptibility contrast between frozen and unfrozen tissue disturbs the local magnetic field in the proximity of the ice-ball during cryotherapy. This effect should be corrected for in real time to allow PRFS-based monitoring of near-zero temperatures during intervention. Susceptibility artifacts were corrected post-processing, using a rapid numerical algorithm. The difference in bulk magnetic susceptibility between frozen and non-frozen tissue was approximated to be uniform over the ice-ball volume and was determined from the isothermal principle applied to the phase-transition frontier of compartments. Subsequently, the magnetic perturbation field was calculated rapidly in 3D using a Fourier-convolution. Experimental studies were performed for two scenarios: tissue defrosting in a water bath and induction of an ice-ball by a MR-compatible cryogenic probe. The susceptibility artifacts yielded PRFS temperature errors as high as 10-12°C proximal to the ice-ball, positive or negative depending on the relative orientation of the position vector from the B(o) direction. These effects were fully corrected for to within the noise range. The susceptibility-corrected PRFS temperature values were consistent with the phase-transition isothermal condition, irrespective of the local orientation of the position vector. By implementing on-line the post processing algorithm, PRFS MRT may be used as a safety tool for non-invasive and accurate monitoring of near-zero temperatures during MR-guided clinical cryotherapy.
    MAGMA Magnetic Resonance Materials in Physics Biology and Medicine 09/2011; 25(1):23-31. · 1.86 Impact Factor
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    ABSTRACT: The authors previously developed magnetic resonance (MR)-trackable magnetocapsules (MCs) that can simultaneously immunoprotect human islet cells and noninvasively monitor portal delivery and engraftment in real time with MR imaging. This study was designed to assess the physiologic effects of the delivery of a clinical dose of MCs (140,000 capsules) into the portal vein (PV) in swine over a 1-month period. MCs were formed by using clinical-grade alginate mixed with a clinically applicable dosage of ferumoxide. Percutaneous access into the PV was obtained by using a custom-built, MR-trackable needle, and 140,000 MCs were delivered under MR guidance in five swine. Portal pressures and liver function data were obtained over a 4-week period. A transient increase in portal pressure occurred immediately after MC delivery that returned to normal levels by 4 weeks after MC delivery. Liver function test results were normal during the entire period, and the appearance of the MCs on MR imaging did not change. A clinically applicable dose of 140,000 MCs has no adverse effects on portal pressures or liver function in this normal swine model during the first month after delivery.
    Journal of vascular and interventional radiology: JVIR 09/2011; 22(9):1335-40. · 1.81 Impact Factor
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    ABSTRACT: Understanding how individual cells behave inside living systems will help enable new diagnostic tools and cellular therapies. Superparamagnetic iron oxide particles can be used to label cells and theranostic capsules for noninvasive tracking using MRI. Contrast changes from superparamagnetic iron oxide are often subtle relative to intrinsic sources of contrast, presenting a detection challenge. Here, we describe a versatile postprocessing method, called Phase map cross-correlation Detection and Quantification (PDQ), that automatically identifies localized deposits of superparamagnetic iron oxide, estimating their volume magnetic susceptibility and magnetic moment. To demonstrate applicability, PDQ was used to detect and characterize superparamagnetic iron oxide-labeled magnetocapsules implanted in porcine liver and suspended in agarose gel. PDQ was also applied to mouse brains infiltrated by MPIO-labeled macrophages following traumatic brain injury; longitudinal, in vivo studies tracked individual MPIO clusters over 3 days, and tracked clusters were corroborated in ex vivo brain scans. Additionally, we applied PDQ to rat hearts infiltrated by MPIO-labeled macrophages in a transplant model of organ rejection. PDQ magnetic measurements were signal-to-noise ratio invariant for images with signal-to-noise ratio > 11. PDQ can be used with conventional gradient-echo pulse sequences, requiring no extra scan time. The method is useful for visualizing biodistribution of cells and theranostic magnetocapsules and for measuring their relative iron content. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.
    Magnetic Resonance in Medicine 06/2011; 67(1):278 - 289. · 3.27 Impact Factor
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    ABSTRACT: OBJECTIVE: The purpose of this article is to provide a preliminary user assessment of Image-Overlay, an augmented reality system for MRI-guided needle placement, in a spine phantom. CONCLUSION: Image-Overlay can be used to successfully target lumbar facet joints with high accuracy and minimal insertions. This is potentially useful for other interventional MRI applications. Additional clinical assessment is needed.
    American Journal of Roentgenology 03/2011; 196(3):W305-7. · 2.90 Impact Factor
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    ABSTRACT: To assess the feasibility, precision, and accuracy of real-time temperature mapping (TMap) during laser-induced thermotherapy (LITT) for clinical practice in patients liver with a gradient echo (GRE) sequence using the proton resonance frequency (PRF) method. LITT was performed on 34 lesions in 18 patients with simultaneous real-time visualization of relative temperature changes. Correlative contrast-enhanced T1-weighted magnetic resonance (MR) images of the liver were acquired after treatment using the same slice positions and angulations as TMap images acquired during LITT. For each slice, TMap and follow-up images were registered for comparison. Afterwards, segmentation based on temperature (T) >52°C on TMap and based on necrosis seen on follow-up images was performed. These segmented structures were overlaid and divided into zones where the TMap was found to either over- or underestimate necrosis on the postcontrast images. Regions with T>52°C after 20 minutes were defined as necrotic tissue based on data received from two different thermal dose models. The average intersecting region of TMap and necrotic zone was 87% ± 5%, the overestimated 13% ± 4%, and the underestimated 13% ± 5%. This study demonstrates that MR temperature mapping appears reasonably capable of predicting tissue necrosis on the basis of indicating regions having greater temperatures than 52°C and could be used to monitor and adjust the thermal therapy appropriately during treatment.
    Journal of Magnetic Resonance Imaging 03/2011; 33(3):704-12. · 2.57 Impact Factor
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    ABSTRACT: To compare magnetic resonance (MR) thermometry based on the proton resonance frequency (PRF) method using a single shot echoplanar imaging (ss EPI) sequence to both of the standard sequences, gradient echo (GRE) and segmented echoplanar imaging (seg EPI) in the in vivo human brain, at 1.5T and 3T. Repetitive MR thermometry was performed on the brain of six volunteers using GRE, seg EPI, and ss EPI sequences on whole-body 1.5T and 3T clinical systems using comparable acquisition parameters. Phase stability and temperature data precision in the human head were determined over 12 min for the three sequences at both field strengths. An ex-vivo swine skeletal muscle model was used to evaluate temperature accuracy of the ss EPI sequence during heating by high intensity focused ultrasound (HIFU). In-vivo examinations of brain revealed an average temperature precision of 0.37 °C/0.39 °C/0.16 °C at 3T for the GRE/seg EPI/ss EPI sequences. At 1.5T, a precision of 0.58 °C/0.63 °C/0.21 °C was achieved. In the ex-vivo swine model, a strong correlation of temperature data derived using ss EPI and GRE sequences was found with a temperature deviation <1 °C. The ss EPI sequence was the fastest and the most precise sequence for MR thermometry, with significantly higher accuracy compared to GRE.
    Physica Medica 10/2010; 26(4):192-201. · 1.17 Impact Factor
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    ABSTRACT: Repetitive MR thermometry was performed on the brain of nine volunteers using GRE, seg EPI, and ss EPI sequences on whole-body 1.5 T and 3 T clinical systems using comparable acquisition parameters. Phase stability and temperature data precision in the human head were determined over 12 minutes for the three sequences at both field strengths. The ss EPI sequence was the fastest and the most precise sequence for MR thermometry, with significantly higher accuracy compared to GRE. An ex-vivo swine skeletal muscle model was used to evaluate temperature accuracy of the ss EPI sequence during heating by high intensity focused ultrasound (HIFU).
    03/2010;
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    ABSTRACT: Radiologic manifestations of X-linked chondrodysplasia punctata (CDPX1) typically include chondrodysplasia, epiphyseal stippling, punctate calcification of cartilage, distal phalangeal hypoplasia, and nasal/midface hypoplasia. We present an infant with CDPX1 demonstrating calcification and stenosis of the entire trachea and mainstem bronchi, as well as possible anterior C1 subluxation due to progression of congenital vertebral dysplasia.
    Pediatric Radiology 03/2009; 39(6):625-8. · 1.57 Impact Factor
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    ABSTRACT: Pelvic arteriovenous malformation (AVM) is a rare condition in which a section of blood vessels lacks a capillary network, resulting in blood from an artery being delivered directly to a vein. This condition may be congenital or acquired. Percutaneous selective embolization can obliterate AVMs and has increasingly been used for management. Management involves transcatheter embolization with either inert glues, balloons, or fibered titanium coils that are designed to limit the flow through feeding vessels. We describe one potential complication of transcatheter embolization that involves necrosis of the bladder wall with a novel technique for endoscopic management of an extruded coil in the bladder.
    Journal of endourology / Endourological Society 08/2008; 22(7):1527-9. · 1.75 Impact Factor

Publication Stats

277 Citations
93.18 Total Impact Points

Institutions

  • 2005–2014
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, Maryland, United States
  • 2013
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      Erlangen, Bavaria, Germany
  • 2004–2009
    • Johns Hopkins Medicine
      • Department of Radiology and Radiological Science
      Baltimore, MD, United States