Correlation between quantitative whole-body muscle magnetic resonance imaging and clinical muscle weakness in Pompe disease.

INTRODUCTION: Previous examination of whole-body muscle involvement in Pompe disease has been limited to physical examination and/or qualitative magnetic resonance imaging (MRI). In this study we assess the feasibility of quantitative proton-density fat-fraction (PDFF) whole-body MRI in late-onset Pompe disease (LOPD) and compare the results with manual muscle testing. METHODS: Seven LOPD patients and 11 disease-free controls underwent whole-body PDFF MRI. Quantitative MR muscle group assessments were compared with physical testing of muscle groups. RESULTS: The 95% upper limits of confidence intervals for muscle groups were 4.9-12.6% in controls and 6.8-76.4% in LOPD patients. LOPD patients showed severe and consistent tongue and axial muscle group involvement, with less marked involvement of peripheral musculature. MRI was more sensitive than physical examination for detection of abnormality in multiple muscle groups. CONCLUSION: This integrated, quantitative approach to muscle assessment provides more detailed data than physical examination and may have clinical utility for monitoring disease progression and treatment response.

Venous filling defects on portal venous phase CT of the abdomen and pelvis: clinical implications and positive predictive value for diagnosing deep venous thrombosis.

PURPOSE: To determine the prevalence, resulting clinical decisions, and the positive predictive value (PPV) of venous filling defects detected on portal venous phase (PVP) CT. METHODS: Over a 3-year period, 42412 consecutive patients underwent a PVP abdominopelvic CT; of these, 348 reports mentioned a filling defect concerning for deep venous thrombosis (DVT) in the IVC, iliac, or common femoral veins. Ninety-three patients underwent a reference standard venous imaging study. RESULTS: The prevalence of venous filling defects in CT reports was 0.82% (n = 348). Reports worded with higher degrees of certainty were statistically more likely to result in treatment, while lower certainty was correlated with additional confirmatory imaging. The PPV for detection of DVT was 77%. The presence of peri-vascular stranding or vessel expansion increased the PPV of PVP CT to 95% and 100%, respectively. CONCLUSION: While the PPV for filling defects on PVP CT was modest, it was substantially improved if peri-venous stranding or vessel expansion was present.

Comparison of primary jejunostomy tubes versus gastrojejunostomy tubes for percutaneous enteral nutrition.

PURPOSE: To evaluate technical success and long-term outcomes of percutaneous primary jejunostomy tubes for postpyloric enteral feeding compared with percutaneous gastrojejunostomy (GJ) tubes. MATERIALS AND METHODS: Over a 25-month interval, 41 consecutive patients (26 male; mean age, 55.9 y) underwent attempted fluoroscopy-guided direct percutaneous jejunostomy tube insertion. Insertions at previous jejunostomy tube sites were excluded. The comparison group consisted of all primary GJ tube insertions performed over a 12-month interval concomitant with the jejunostomy tube interval (N = 169; 105 male; mean age, 59.4 y). Procedural, radiologic, and clinical data were retrospectively reviewed. Intervention rates were expressed as events per 100 catheter-days. RESULTS: The technical success rate for percutaneous jejunostomy tube insertion was 96%, versus 93% for GJ tubes (P = .47). Mean fluoroscopy times were similar for jejunostomy and GJ tubes (9.8 vs 10.0 min, respectively; P value not significant). Jejunostomy tubes exhibited a lower rate of catheter dysfunction than GJ tubes, with catheter exchange rates of 0.24 versus 0.93, respectively, per 100 catheter-days (P = .045). GJ tube tip retraction into the stomach occurred in 9.5% of cases, at a rate of 0.21 per 100 catheter-days. Intervention rates related to leakage were 0.19 and 0.03 for jejunostomy and GJ tubes, respectively (P < .01). Jejunostomy and GJ tubes exhibited similar rates of catheter exchange for occlusion and replacement as a result of inadvertent removal. No major complications were encountered in either group. CONCLUSIONS: Percutaneous insertion of primary jejunostomy tubes demonstrated technical success and complication rates similar to those of GJ tubes. Jejunostomy tubes exhibited a lower dysfunction rate but a higher leakage rate compared with GJ tubes.

Tunneled internal jugular hemodialysis catheters: impact of laterality and tip position on catheter dysfunction and infection rates.

PURPOSE: To determine rates of dysfunction and infection for tunneled internal jugular vein hemodialysis catheters based on laterality of insertion and catheter tip position. MATERIALS AND METHODS: Retrospective review of a procedural database for tunneled internal jugular vein hemodialysis catheter placements between January 2008 and December 2009 revealed 532 catheter insertions in 409 patients (234 male; mean age, 54.9 y). Of these, 398 catheters were placed on the right and 134 on the left. The catheter tip location was categorized as superior vena cava (SVC), pericavoatrial junction, or mid- to deep right atrium based on review of the final intraprocedural radiograph. The rates of catheter dysfunction and catheter-related infection (reported as events per 100 catheter-days) were analyzed. RESULTS: Catheters terminating in the SVC or pericavoatrial junction inserted from the left showed significantly higher rates of infection (0.50 vs 0.27; P = .005) and dysfunction (0.25 vs 0.11; P = .036) compared with those inserted from the right. No difference was identified based on laterality for catheter tip position in the mid- to deep right atrium. Left-sided catheters terminating in the SVC or pericavoatrial junction had significantly more episodes of catheter dysfunction or infection than catheters terminating in the mid- to deep right atrium (0.84 vs 0.35; P = .006), whereas no significant difference was identified for right-sided catheters based on tip position. CONCLUSIONS: When inserted from the left internal jugular vein, catheter tip position demonstrated a significant impact on catheter-related dysfunction and infection; this relationship was not demonstrated for right-sided catheters.

Generating color-coded anatomic muscle maps for correlation of quantitative magnetic resonance imaging analysis with clinical examination in neuromuscular disorders.

INTRODUCTION: Fatty infiltration of muscles may be seen in many neuromuscular disorders, including glycogen storage disease (GSD), muscular dystrophy, and amyotrophic lateral sclerosis. Recording pathologic involvement of musculature in these patients is cumbersome, given marked disease heterogeneity within each individual. We describe a novel method for simplifying this process and present its application in a patient with GSD type IIIa. METHODS: A color-coded visual mapping tool was developed based on a commonly used spreadsheet platform. RESULTS: This tool depicts individual muscle groups as shapes linked to data cells corresponding to quantitative MRI-based measures of fatty infiltration and weakness assessed by physical examination. It allows for rapid evaluation and chronological comparison of all mapped muscle groups on a single graphical sheet, as well as assessment of response to therapy. CONCLUSION: This approach can be applied in any neuromuscular disorder where muscle function is assessed by clinical or imaging scores.

Abdominopelvic and lower extremity deep venous thrombosis: evaluation with contrast-enhanced MR venography with a blood-pool agent.

OBJECTIVE: The purpose of this article is to evaluate contrast-enhanced (CE) MR venography (MRV) with a blood-pool agent for detection of abdominopelvic and lower extremity deep venous thrombosis (DVT) compared with a conventional unenhanced gradient-recalled echo (GRE) MRV technique. MATERIALS AND METHODS: This retrospective study was performed on 30 patients (mean age, 52.7 years; 15 men and 15 women) referred for MRV between March 2010 and November 2010 for evaluation of lower extremity or abdominopelvic DVT. All patients underwent a GRE sequence followed by a CE T1-weighted sequence with gadofosveset, a blood-pool agent. The abdominopelvic and lower extremity venous system was divided into 13 segments. The presence of acute or chronic DVT was assessed by six radiologists, as well as qualitative and quantitative assessments of each venous segment. Image acquisition and interpretation times were also tabulated. RESULTS: The sensitivity and specificity for acute DVT were 91.0% and 99.8%, respectively, on CE MRV compared with 80.8% and 95.8%, respectively, on GRE MRV (p = 0.077 and p < 0.001). The sensitivity and specificity for chronic DVT were 84.4% and 98.4%, respectively, on CE MRV and 64.5% and 95.6%, respectively, on GRE MRV (p < 0.001 for both). Subjective ratings of vein visualization, signal homogeneity, and confidence pertaining to DVT diagnosis were significantly higher with the CE images (p < 0.001). The contrast-to-noise ratio for CE images was similar or significantly higher for all venous segments. Image acquisition and radiologist interpretation times on the CE studies were decreased (p < 0.001). CONCLUSION: Gadofosveset-enhanced MRV had equal or higher sensitivity and specificity for detection of DVT than did GRE MRV, with decreased time for image acquisition and interpretation.

Covered transjugular intrahepatic portosystemic shunts: accuracy of ultrasound in detecting shunt malfunction.

OBJECTIVE: The purpose of this study was to determine the accuracy of ultrasound for detecting transjugular intrahepatic portosystemic shunt (TIPS) malfunction in covered stents in comparison with bare metal stents. MATERIALS AND METHODS: During a 6-year period, 126 TIPS angiography examinations were performed in 78 patients who had undergone a recent TIPS ultrasound examination. Radiology reports and images were retrospectively reviewed, and the sensitivity and specificity of sonographic parameters for detecting TIPS dysfunction were calculated using TIPS angiography and portosystemic gradient as the reference standards. RESULTS: Of 126 paired studies, 43 were in bare metal TIPS and 83 were in covered TIPS. Peak shunt velocity of covered and bare metal TIPS measured by ultrasound showed comparable sensitivities for detection of shunt dysfunction, using both depressed (< 90 cm/s) and elevated (> 200 cm/s) peak shunt velocity criteria. However, a depressed velocity was more specific in covered TIPS (0.939 vs 0.550, p < 0.001) whereas elevated velocity was more specific in bare TIPS (0.485 vs 0.800, p = 0.041). An interval change in peak TIPS velocity greater than 25% was significantly more sensitive in detection of dysfunction in covered TIPS (0.815 vs 0.400, p = 0.015) whereas detection based on main portal vein velocities (≤ 30 cm/s) was not statistically different in the two groups. CONCLUSION: Our data suggest that the accuracy of ultrasound for detection of TIPS shunt malfunction is at least as high in covered stents as in bare metal stents. Diagnostic performance for several sonographic parameters varied significantly between bare and covered stents, suggesting the need for optimization of sonographic criteria for covered stents.

Reproducibility of dynamic contrast-enhanced MR imaging. Part II. Comparison of intra- and interobserver variability with manual region of interest placement versus semiautomatic lesion segmentation and histogram analysis.

PURPOSE: To compare the inter- and intraobserver variability with manual region of interest (ROI) placement versus that with software-assisted semiautomatic lesion segmentation and histogram analysis with respect to quantitative dynamic contrast material-enhanced (DCE) MR imaging determinations of the volume transfer constant (K(trans)). MATERIALS AND METHODS: The study was approved by the institutional review board and compliant with HIPAA. The requirement to obtain informed consent was waived. Fifteen DCE MR imaging studies of the female pelvis defined the study group. Uterine fibroids were used as a perfusion model. Three varying types of lesion measurements were performed by five readers on each study by using DCE MR imaging perfusion analysis software with manual ROI placement and a semiautomatic lesion segmentation and histogram analysis solution. Intra- and interreader variability of measurements of K(trans) with the different measurement types was calculated. RESULTS: The overall interobserver variability of K(trans) with manual ROI placement (mean, 28.5% ± 9.3) was reduced by 42.5% when the semiautomatic, software-assisted lesion measurement method was used (16.4% ± 6.2). Whole-lesion measurement showed the lowest interobserver variability with both measurement methods (20.1% ± 4.3 with the manual method vs 10.8% ± 2.6 with the semiautomatic method). The overall intrareader variability with the manual ROI method (7.6% ± 10.6) was not significantly different from that with the semiautomatic method (7.3% ± 10.8), but the intraclass correlation coefficient for intrareader reproducibility improved from 0.86 overall with the manual method to 0.99 with the semiautomatic method. CONCLUSION: A semiautomatic lesion segmentation and histogram analysis approach can provide a significant reduction in interobserver variability for DCE MR imaging measurements of K(trans) when compared with manual ROI methods, whereas intraobserver reproducibility is improved to some extent.

Reproducibility of dynamic contrast-enhanced MR imaging. Part I. Perfusion characteristics in the female pelvis by using multiple computer-aided diagnosis perfusion analysis solutions.

PURPOSE: To test the reproducibility of model-derived quantitative and semiquantitative pharmacokinetic parameters among various commercially available perfusion analysis solutions for dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was institutional review board approved and HIPAA compliant, with waiver of informed consent granted. The study group consisted of 15 patients (mean age, 44 years; range, 28-60 years), with 15 consecutive 1.5-T DCE MR imaging studies performed between October 1, 2010, and December 27, 2010, prior to uterine fibroid embolization. Studies were conducted by using variable-flip-angle T1 mapping and four-dimensional, time-resolved MR angiography with interleaved stochastic trajectories. Images from all DCE MR imaging studies were postprocessed with four commercially available perfusion analysis solutions by using a Tofts and Kermode model paradigm. Five observers measured pharmacokinetic parameters (volume transfer constant [K(trans)], v(e) [extracellular extravascular volume fraction], k(ep)[K(trans)/v(e)], and initial area under the gadolinium curve [iAUGC]) three times for each imaging study with each perfusion analysis solution (between March 13, 2011, and September 8, 2011) by using two different region-of-interest methods, resulting in 1800 data points. RESULTS: After normalization of data output, significant differences in mean values were found for the majority of perfusion analysis solution combinations. The within-subject coefficient of variation among perfusion analysis solutions was 48.3%-68.8% for K(trans), 37.2%-60.3% for k(ep), 27.7%-74.1% for v(e), and 25.1%-61.2% for iAUGC. The intraclass correlation coefficient revealed only poor to moderate consistency among pairwise perfusion analysis solution comparisons (K(trans), 0.33-0.65; k(ep), 0.02-0.81; v(e), -0.03 to 0.72; and iAUGC, 0.47-0.78). CONCLUSION: A considerable variability for DCE MR imaging pharmacokinetic parameters (K(trans), k(ep), v(e), iAUGC) was found among commercially available perfusion analysis solutions. Therefore, clinical comparability across perfusion analysis solutions is currently not warranted. Agreement on a postprocessing standard is paramount prior to establishing DCE MR imaging as a widely incorporated biomarker.

Inter- and intra-rater reproducibility of quantitative dynamic contrast enhanced MRI using TWIST perfusion data in a uterine fibroid model.

PURPOSE: To determine the reproducibility of TWIST-derived (Time-Resolved Angiography with Interleaved Stochastic Trajectories) quantitative dynamic contrast enhanced (DCE) MRI in a uterine fibroid model. MATERIALS AND METHODS: The institutional review board approved this retrospective study. Dynamic contrast-enhanced TWIST datasets from 15 randomly selected 1.5 Tesla pelvic MR studies were postprocessed. Five readers recorded kinetic parameters (K(trans) [volume transfer constant], ve [extracellular extravascular space volume], kep [flux rate constant], iAUC [initial area under the gadolinium-time curve]) of the largest uterine fibroid using three region-of-interest (ROI) selection methods. Measurements were randomized and repeated three times, and measures of reproducibility were calculated. RESULTS: The intra-rater coefficients of variation (CVs, brackets indicate 95% confidence intervals) varied from 4.6% to 7.6% (K(trans) 7.6% [6.1%, 9.1%], kep 7.2% [5.9%, 8.5%], ve 4.6% [3.8%, 5.4%], and iAUC 7.2% [6.1%, 8.3%]). ve was the most reproducible (P < 0.05). Inter-rater reproducibility was significantly (P < 0.05) greater for the large ROI method (range of intraclass correlation coefficients [ICCs] = 0.80-0.98 versus 0.48-0.63 [user-defined ROI] versus 0.41-0.69 [targeted ROI]). The uterine fibroid accounted for the greatest fraction of variance for the large ROI method (range across kinetic parameters: 83-98% versus 56-69% [user-defined ROI] versus 47-74% [targeted ROI]). The reader accounted for the greatest fraction of variance for the user-defined ROI method (0.4-14.1% versus 0.1-3.0% [large ROI] versus <0.1-1.5% [targeted ROI]). CONCLUSION: Changes in TWIST-derived DCE-MRI kinetic parameters of up to 9-15% may be attributable to measurement error. Large DCE-MRI regions of interest are the most reproducible across multiple readers.

Bulbar muscle weakness and fatty lingual infiltration in glycogen storage disorder type IIIa.

Glycogen storage disorder type III (GSD III) is a rare autosomal recessive disorder resulting from a deficiency of glycogen debranching enzyme, critical in cytosolic glycogen degradation. GSD IIIa, the most common form of GSD III, primarily affects the liver, cardiac muscle, and skeletal muscle. Although skeletal muscle weakness occurs commonly in GSD IIIa, bulbar muscle involvement has not been previously reported. Here we present three GSD IIIa patients with clinical evidence of bulbar weakness based on instrumental assessment of lingual strength. Dysarthria and/or dysphagia, generally mild in severity, were evident in all three individuals. One patient also underwent correlative magnetic resonance imaging (MRI) which was remarkable for fatty infiltration at the base of the intrinsic tongue musculature, as well as abnormal expansion of the fibro-fatty lingual septum. Additionally, we provide supportive evidence of diffuse glycogen infiltration of the tongue at necropsy in a naturally occurring canine model of GSD IIIa. While further investigation in a larger group of patients with GSD III is needed to determine the incidence of bulbar muscle involvement in this condition and whether it occurs in GSD IIIb, clinical surveillance of lingual strength is recommended.

Gradient shimming during magnetic resonance imaging of the liver: comparison of a standard protocol versus a novel reduced protocol.

PURPOSE: The aim of this study was to examine the effect of minimizing prescan adjustments on table time and image quality in magnetic resonance imaging (MRI) of the liver. MATERIALS AND METHODS: This prospective Health Insurance Portability and Accountability Act-compliant study was approved by the institutional review board, and written informed consent was obtained. Ten volunteers were imaged twice using a noncontrast liver MRI protocol consisting of a total of 10 pulse sequences, once with a standard protocol and once with a fixed table position/minimized prescan adjustment protocol (in random order). Total examination time was evaluated according to a Lean Six Sigma framework. Quantitative sequences, including diffusion-weighted imaging with apparent diffusion coefficient, multi-echo Dixon fat percentage, and the transverse relaxation time, were evaluated and compared between the two protocols. Two experienced readers, blinded to the protocol used, compared image quality between the two protocols. RESULTS: The average number of prescan adjustment steps per examination was reduced from 58.0 to 22.1 using the minimal shimming protocol compared with the normal shimming protocol (P < 0.001). Mean business value added time (scan preparatory time) was reduced by 58% (3 minutes 3 seconds vs 7 minutes 13 seconds), whereas mean total examination time was 20% lower (18 minutes 13 seconds vs 22 minutes 48 seconds, P < 0.001). Quantitative measures obtained using the two protocols were equivalent, and neither reader detected a significant difference in subjective image quality. CONCLUSION: Fixing table position minimizes prescan adjustments and reduces total table time in liver MRI without adversely affecting image quality.

Global health training in radiology residency programs.

RATIONALE AND OBJECTIVES: To measure perceptions of radiology residents regarding the imaging needs of the developing world and the potential role of an organized global health imaging curriculum during residency training. MATERIALS AND METHODS: An electronic survey was created and then distributed to residents in accredited US radiology residency. RESULTS: Two hundred ninety-four residents responded to the survey. A majority (61%) planned to pursue future international medical aid work, even though a similar proportion (59%) believed that they would be ill-prepared with their current training to pursue this career goal. The vast majority (91%) of respondents stated that their residency program offers no opportunities to participate in global health imaging experiences. Most surveyed residents felt that an organized global health imaging curriculum would improve understanding of basic disease processes (87%) and cost-conscious care (82%), prepare residents for lifelong involvement in global health (80%), and increase interpretative skills in basic radiology modalities (73%). If such a curriculum were available, most (62%) of surveyed residents stated that they would be likely or very likely to participate. Many (58%) believed the availability of such a program would have influenced their choice of residency program; a similar proportion of residents (75%) believed that the availability of a global health imaging curriculum would increase recruitment to the field of radiology. CONCLUSION: Many radiology residents are motivated to acquire global health imaging experience, with most survey respondents planning to participate in global health initiatives. These data demonstrate an imbalance between the level of resident interest and the availability of global health imaging opportunities, and support the need for discussion on how to implement global health imaging training within radiology residency programs.

Antigen delivery by alpha(2)-macroglobulin enhances the cytotoxic T lymphocyte response.

alpha(2)M* targets antigens to APCs for rapid internalization, processing, and presentation. When used as an antigen-delivery vehicle, alpha(2)M* amplifies MHC class II presentation, as demonstrated by increased antibody titers. Recent evidence, however, suggests that alpha(2)M* encapsulation may also enhance antigen-specific CTL immunity. In this study, we demonstrate that alpha(2)M*-delivered antigen (OVA) enhances the production of specific in vitro and in vivo CTL responses. Murine splenocytes expressing a transgenic TCR specific for CTL peptide OVA(257-264) (SIINFEKL) demonstrated up to 25-fold greater IFN-gamma and IL-2 secretion when treated in vitro with alpha(2)M*-OVA compared with soluble OVA. The frequency of IFN-gamma-producing cells was increased approximately 15-fold, as measured by ELISPOT. Expansion of the OVA-specific CD8+ T cell population, as assayed by tetramer binding and [3H]thymidine incorporation, and OVA-specific cell-mediated cytotoxicity, as determined by a flow cytometric assay, were also enhanced significantly by alpha(2)M*-OVA. Furthermore, significant CTL responses were observed at antigen doses tenfold lower than those required with OVA alone. Finally, we also observed enhanced humoral and CTL responses by naïve mice following intradermal immunization with alpha(2)M*-OVA. These alpha(2)M*-OVA-immunized mice demonstrated increased protection against a s.c.-implanted, OVA-expressing tumor, as demonstrated by delayed tumor growth and prolonged animal survival. The observation that alpha(2)M*-mediated antigen delivery elicits specific CTL responses suggests the cross-presentation of antigen onto MHC class I. These results support alpha(2)M* as an effective antigen-delivery system that may be particularly useful for vaccines based on weakly immunogenic subunits or requiring dose sparing.