A homozygous splice variant in ATP5PO, disrupts mitochondrial complex V function and causes Leigh syndrome in two unrelated families.

Mitochondrial complex V plays an important role in oxidative phosphorylation by catalyzing the generation of ATP. Most complex V subunits are nuclear encoded and not yet associated with recognized Mendelian disorders. Using exome sequencing, we identified a rare homozygous splice variant (c.87+3A>G) in ATP5PO, the complex V subunit which encodes the oligomycin sensitivity conferring protein, in three individuals from two unrelated families, with clinical suspicion of a mitochondrial disorder. These individuals had a similar, severe infantile and often lethal multi-systemic disorder that included hypotonia, developmental delay, hypertrophic cardiomyopathy, progressive epileptic encephalopathy, progressive cerebral atrophy, and white matter abnormalities on brain MRI consistent with Leigh syndrome. cDNA studies showed a predominant shortened transcript with skipping of exon 2 and low levels of the normal full-length transcript. Fibroblasts from the affected individuals demonstrated decreased ATP5PO protein, defective assembly of complex V with markedly reduced amounts of peripheral stalk proteins, and complex V hydrolytic activity. Further, expression of human ATP5PO cDNA without exon 2 (hATP5PO-∆ex2) in yeast cells deleted for yATP5 (ATP5PO homolog) was unable to rescue growth on media which requires oxidative phosphorylation when compared to the wild type construct (hATP5PO-WT), indicating that exon 2 deletion leads to a non-functional protein. Collectively, our findings support the pathogenicity of the ATP5PO c.87+3A>G variant, which significantly reduces but does not eliminate complex V activity. These data along with the recent report of an affected individual with ATP5PO variants, add to the evidence that rare biallelic variants in ATP5PO result in defective complex V assembly, function and are associated with Leigh syndrome.

Reliability of 3 Strategies of Orbital Tumor Volume Measurement Using Phantom Modeling.

PURPOSE: The reliability of 3 volume measurement strategies was investigated using MRI and a simple method for creating phantom orbit tumors. METHODS: Water-based starch was molded into orbital "tumors" of 3 shapes (sphere, ovoid, diffuse); water displacement was used to calculate volume. "Tumors" were placed into 3D-printed orbit phantoms, MRIs were obtained and volume analysis was performed. Observers measured tumor volume using ellipsoid volume (EV), manual segmentation, and semi-automated segmentation strategies. Intraclass correlation coefficients were calculated comparing observer measurements to true volumes. The coefficient of repeatability determined the percentage of tumor volume change required for each method to detect tumor growth. RESULTS: Intraclass correlation coefficients comparing measured volumes to true volumes using EV, manual segmentation, and semi-automated segmentation were 0.61, 0.98, and 0.99 for spherical, 0.64, 0.97, and 0.98 for ovoid, and 0.18, 0.82, and 0.87 for diffuse tumors. Semi-automated segmentation followed by manual segmentation had the highest correlation between measured and true tumor volume for all 3 tumor geometries. EV had low correlation with true volume for all tumor geometries. Diffuse tumors had high variability and low correlation for all 3 measurement techniques. CONCLUSIONS: This study shows the reliability of 3 strategies to measure orbital tumor volume with MRI based on tumor geometry, using a simple phantom model. EV, the most commonly employed strategy in clinical practice, had low correlation and high variability across tumor shapes. Using manual segmentation and semi-automated segmentation, a measured change in volume greater than 25% may be considered true growth, while the EV strategy required a 40%-400% change in volume to reliably measure tumor growth.

3D Printing and Heart Failure: The Present and the Future.

Advanced imaging modalities provide essential anatomic and spatial information in patients with complex heart disease. Two-dimensional imaging can be limited in the extent to which true 3-dimensional (3D) relationships are represented. The application of 3D printing technology has increased the creation of physical models that overcomes the limitations of a 2D screen. Many groups have reported the use of 3D printing for preprocedural planning in patients with different causes of heart failure. This paper reviews the innovative applications of this technique to provide patient-specific models to improve patient care.

Virtual septal myectomy for preoperative planning in hypertrophic cardiomyopathy.

OBJECTIVE: Although septal myectomy (SM) is the preferred treatment for medication-refractory obstructive hypertrophic cardiomyopathy, the procedure remains subjective. We have developed a virtual myectomy (VM) technique using 3-dimensional reconstruction of gated cardiac computed tomography (CT) to assist intraoperative objective assessment of the adequacy of the resection. METHODS: We retrospectively reviewed patients 15 patients who underwent a SM guided by preoperative VM at our program between March 2016 and July 2017. Gated cardiac CT was performed to allow delineation of the left ventricular (LV) myocardium at end-diastole to replicate the cardioplegic myocardial arrest (90%-95% RR interval). SM was performed to attain resection volume predicted by VM. Retrospective, blinded VM also was performed with fixed parameters to determine relationship between ideal (VM1) and conservative (VM2) VM and actual resection. RESULTS: Mean patient age was 52.1 ± 10.6 years, 27% were male, and 80% had New York Heart Association class 3 or 4. Preoperative mean peak LV outflow tract gradient was 79 mm Hg (range 47-82). In-hospital mortality was 0%. Mean postoperative LV outflow tract gradient was 13 mm Hg (11-19). Gated cardiac CT was performed with mean phase 94% (86%-98%). Mean total LV myocardial volume was 226 cm3 (146-365) and volume of the asymmetric portion of the LV was 19 cm3 (5.2-48.8). Actual surgical resection volume was 6.2 ± 1.7 cm3. Retrospective VM1 and VM2 performed postoperatively blinded to surgical results were 12.8 cm3 (4.8-29.23) and 6.7 cm3 (3.5-13.2), showing a modest correlation (R1 = 0.44, R2 = 0.56) with actual myectomy. CONCLUSIONS: Three-dimensional CT and VM can be a viable addition to preoperative assessment of patients with obstructive hypertrophic cardiomyopathy.

CT colonography features of sigmoid diverticular disease.

OBJECTIVE: The objective of this study is to assess the sigmoid distensibility during CT colonography (CTC) in patients with diverticular disease. METHODS: Consecutive patients without a history of pelvic radiation or neoplasms underwent 150 CTC. Three radiologists in consensus evaluated axial images for colonic distention, luminal diameters (mm), diverticula, and muscular thickening. RESULTS: The minimum colon diameter in patients with muscular thickening was significantly smaller, irrespective of the presence of diverticula (P=.009). CONCLUSION: Muscular thickening with diverticular disease was associated with significantly less sigmoid colon distension.

Utility of an informational intranet in a radiology department.

RATIONALE AND OBJECTIVES: The authors performed this study to assess the usefulness of the various features of their radiology department intranet and to quantify its effect in facilitating intradepartmental information flow. MATERIALS AND METHODS: The number, length, and nature of visits to each directory on the intranet were recorded by a commercially available intranet analysis software package. RESULTS: During the last 6 months of 2001, 89,411 page views (mean, 485 per day) occurred during 26,344 visits to the radiology department intranet. The most commonly accessed features were billing code lists (29% of total views); the intranet home page (27%); faculty telephone and pager numbers (2.6%); digital dictation access codes (1.6%); and magnetic resonance imaging protocols (1.5%). A total of 32,408 files, including daily clinical assignments, monthly fellow and resident schedules, and protocol forms, were downloaded as portable document files by intranet users. CONCLUSION: The intranet has proved an invaluable addition to the authors' departmental infrastructure, as evidenced by its extensive use by the staff. It has facilitated the rapid dissemination of information without hard copy.

Pulmonary metastases: effect of CT section thickness on measurement--initial experience.

PURPOSE: To assess the effect of commonly used computed tomographic (CT) section thicknesses on metastatic tumor measurements calculated with unidimensional, bidimensional, area, and volumetric methods. MATERIALS AND METHODS: Analysis and data collection were approved by the Institutional Review Board, with waived informed patient consent. Forty-two pulmonary metastases in 10 patients (three men and seven women; age range, 43-83 years; mean age, 65.4 years) were analyzed on CT scans obtained with 3.75-, 5.0-, and 7.5-mm section thicknesses. The lesions were automatically delineated by using a three-dimensional multicriteria segmentation algorithm. Unidimensional (the largest diameter), bidimensional (the product of the two maximal perpendicular diameters), maximal cross-sectional area, and volumetric measurements were automatically obtained for each pulmonary lesion on each section thickness. Means and variances were calculated, and the differences across the three section thicknesses for each of the four measurements were studied by using linear mixed-effects models. The Levene test was used to study the equality of variances. RESULTS: Differences in the means for unidimensional, bidimensional, and area measurements were significant between a section thickness of 3.75 and 5.0 mm (unidimensional, P=.05; bidimensional, P=.05; area, P=.01) and 3.75 and 7.5 mm (unidimensional, P=.06; bidimensional, P=.03; area, P=.02), but not 5.0 and 7.5 mm. There was a significant difference in volumetric measurement as section thickness decreased from 7.5 to 5.0 mm (P <.001) and from 7.5 to 3.75 mm (P <.001). Although there was a slight trend for differences in the variances across section thickness for each measurement, none of the differences were significant. CONCLUSION: Volumetric tumor measurements change with a reduction in section thickness from 7.5 to 5.0 and 3.75 mm. For unidimensional measurement, no change was found when thickness decreased from 7.5 to 5.0 mm.

Quality of virtual colonoscopy in patients who have undergone radiation therapy or surgery: how successful are we?

OBJECTIVE: In patients who have a history of abdominopelvic radiation, surgery, or both, conventional colonoscopy may fail to examine the entire colon. The purpose of this study is to assess whether high-quality virtual colonoscopy can be achieved in this patient population. MATERIALS AND METHODS: After colonic cleansing, 61 patients (16 men and 45 women; mean age, 64 years; age range, 27-81 years) underwent 63 virtual colonoscopy examinations after using either single- or multidetector CT (slice thickness, 3.75-5.0 mm; table speed, 1.7-11.25 cm/sec; pitch, 1.5-3.0; and overlapped reconstructions, 1.95-2.5 cm) in supine and prone positions after IV administration of 1 mg of glucagon and rectal air insufflation. Conventional two-dimensional axial images were analyzed on a PACS (picture archiving and communication system) workstation. Two radiologists, who were unaware of patient history, independently evaluated the colonic distention on a 4-point scale (4 = optimal distention) and fluid retention on a 3-point scale (3 = no fluid) for all segments of the colon in patients who were imaged in both the supine and prone positions. Segmental and total average colon scores were calculated. RESULTS: Forty-one patients (65%; 43 examinations, 67%) underwent prior surgery, radiation, or both (surgery, n = 29; radiation, n = 3; both, n = 11). The average overall colonic distention and fluid retention for this group was 3.13 and 2.38, respectively, versus 3.24 and 2.3 in the control group (p = not significant). CONCLUSION: High-quality examinations were achieved in patients who had previously undergone radiation, surgery, or both with no clinically significant difference in distention or fluid retention compared with the controls.