Clifford R. Weiss

Human bile contains MicroRNA‐laden extracellular vesicles that can be used for cholangiocarcinoma diagnosis

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 because 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. 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 that demonstrated a sensitivity of 67% and specificity of 96%. Importantly, our control group contained 13 PSC patients, 16 with biliary obstruction of varying etiologies (including benign biliary stricture, papillary stenosis, choledocholithiasis, extrinsic compression from pancreatic cysts, and cholangitis), and 3 with bile leak syndromes. Clinically, these types of patients present with a biliary obstructive clinical picture that could be confused with CCA. Conclusion: These findings establish the importance of using extracellular vesicles, rather than whole bile, for developing miR‐based disease markers in bile. Finally, we report on the development of a novel bile‐based CCA diagnostic panel that is stable, reproducible, and has potential clinical utility. (Hepatology 2014;60:896–907)

MR-guided biopsy: A review of current techniques and applications

Biopsy has become a cornerstone of modern medicine and most modern biopsies are performed percutaneously using image guidance, typically computed tomography or ultrasound. MR‐guided biopsy offers many advantages over these more traditional modalities, and the recent development of interventional MR imaging techniques has made MR‐guided percutaneous biopsies and aspirations a clinical reality. As the field of MR‐guided procedures continues to expand and to attract more attention from radiologists, it is important to understand the concepts, techniques, applications, advantages, and limitations of MR‐guided biopsy/percutaneous procedures. Radiologists should also recognize the need for their significant involvement in the technical aspects of MR‐guided procedures, since several user‐defined parameters can alter device visualization in the MR imaging environment and affect procedure safety. This article reviews the prerequisites, systems, and applications of MR‐guided biopsy. J. Magn. Reson. Imaging 2008;27:311–325.

Arterial Wall MRI Characteristics Are Associated With Elevated Serum Markers of Inflammation in Humans

Inflammation contributes to atherosclerosis, but assessment in humans is largely restricted to measurement of markers in blood. We determined whether MRI properties of large arteries were associated with markers of inflammation in serum. Double inversion recovery, fast spin‐echo images of the common carotid arteries and infrarenal aorta were obtained at 1.5 T both before and after gadolinium‐DTPA (0.1 mmol/kg) in 52 subjects ≥40 years of age, 17 of whom had no risk factors for atherosclerosis and thus served as controls. Twenty‐two study participants had increases in wall thickness ( 14 ), T2‐weighted signal intensity ( 11 ), and/or contrast enhancement values ( 7 ) that were >2 standard deviations (SDs) from control group mean values. Ten subjects in this group had evidence of focal plaques in the carotids ( 5 ) and/or aorta ( 6 ). Compared with the remaining 30 subjects, these 22 had significantly higher levels of interleukin‐6 (3.53 ± 2.46 vs. 1.97 ± 1.37 pg/mL, P = 0.004), C‐reactive protein (0.56 ± 0.98 vs. 0.30 ± 0.52 mg/dL, P = 0.019), vascular cell adhesion molecule‐1 (572 ± 153 vs. 471 ± 130 ng/mL, P = 0.012), and intercellular adhesion molecule‐1 (244 ± 80 vs. 202 ± 45 ng/mL, P = 0.015), and nonsignificant differences in levels of E‐selectin (46.1 ± 18.9 vs. 42.3 ± 11.3 ng/mL, P = 0.369). Thus, MRI characteristics of the aorta and carotid arteries were associated with elevated serum markers of inflammation, frequently in the absence of definite atheroma. MRI of large arteries may provide a new approach to investigate the contribution of inflammation to atherogenesis. J. Magn. Reson. Imaging 2001;14:698–704.

Magnetic resonance image-guided trans-septal puncture in a swine heart

To test the feasibility of performing magnetic resonance (MR)‐guided trans‐septal punctures in the swine heart.

Microencapsulated cell tracking

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 1H MRI, 19F 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

Automated detection and characterization of SPIO-labeled cells and capsules using magnetic field perturbations

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.

Augmented Reality Visualization Using Image-Overlay for MR-Guided Interventions: System Description, Feasibility, and Initial Evaluation in a Spine Phantom

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.

Rapid freehand MR-guided percutaneous needle interventions: an image-based approach to improve workflow and feasibility.

To develop and evaluate software‐based methods for improving the workflow of magnetic resonance (MR)‐guided percutaneous interventions.

Endovascular Model of Rabbit Hindlimb Ischemia: A Platform to Evaluate Therapeutic Angiogenesis

PURPOSE Current animal hindlimb ischemia models involve surgical ligation of the femoral artery and delivery of therapeutic angiogenic agents into the adductor compartment. The authors hypothesize that an endovascular model of hindlimb ischemia would be a more appropriate platform, closely resembling atherosclerosis by occluding the vessel from within, causing less inflammation, wound healing and subsequent collateralization. MATERIALS AND METHODS The left superficial femoral artery in 17 rabbits was occluded by endovascular coil embolization (n=9) or surgical ligation (n=8). Animals (n=3; in each group) were sacrificed on day 3 to determine the arteriolar luminal area, number of arterioles, microsphere determined perfusion, and degree of inflammation. On day 28, the remaining animals underwent calf blood pressure measurements and angiography to determine the number of collaterals and diameter of vessels supplying the hindlimb. RESULTS Immediate postprocedure (day 0) and presacrifice (day 3 or 28) occlusion rates were 89% (eight of nine rabbits) and 100% for the endovascular model; 100% and 100% for the surgical model, respectively. Hindlimb paralysis and muscle atrophy was found in one surgical animal. On day 3, there was an increase in hindlimb perfusion (surgery, 0.04+/-0.01; endovascular, 0.02+/-0.01; P=.02), an increase in arteriolar luminal area (surgery, 481 microm+/-240; endovascular, 345 microm+/-151; P=.04), and a trend toward more inflammation (surgery, 5.5+/-3.8; endovascular, 2.5+/-3.0; P=.08) in the surgical group. There was no difference in number of vessels between both groups. On day 28 there was no difference in the calf blood pressure ratios or in the number of collaterals. However, there was enlargement of the distal profunda femoris artery, the vessel closest to the surgical incision, in the surgical group (L/R ratio: immediate post-occlusion, 1.06+/-0.11; day 28, 1.27+/-0.08; P=.02). CONCLUSION The endovascular model was efficacious in providing occlusion of the superficial femoral artery, and induced less of an arteriogenic response compared with the surgical model. The authors believe that this endovascular model is a superior platform for studying therapeutic angiogenic agents.

Review of visceral aneurysms and pseudoaneurysms.

Abstract Abdominal aneurysms and pseudoaneurysms represent an important finding every emergency radiologist must detect. True aneurysms are usually incidental to the presenting complaint, whereas pseudoaneurysms are nearly always symptomatic. We review the demographics, pathophysiology, clinical presentation, computed tomographic appearance, treatment approaches, and prognosis of visceral aneurysms and pseudoaneurysms involving splenic, gastroduodenal, hepatic, superior mesenteric, and renal arteries.