Features associated with clinically actionable hyperechoic hepatic lesions to determine the need for follow-up.

PURPOSE: To evaluate the rate of hyperechoic liver lesions that are clinically actionable and evaluate imaging and clinical factors associated with these to determine the need for follow-up. MATERIALS AND METHODS: This retrospective study included 228 hyperechoic hepatic lesions on ultrasound in 228 patients. Reference standards included either dynamic contrast enhanced MRI (n = 130) or CT (n = 46), follow-up ultrasound performed at least 2 years from baseline (n = 50), or histopathology (n = 2). Three radiologists independently assessed imaging features including lesion orientation, degree of hyper-echogenicity, lesion heterogeneity, and background liver echotexture. Univariable and multivariable logistic regression was used to determine features associated with an actionable hyperechoic lesion. RESULTS: Of the 228 hyperechoic lesions, 14 (6.1%) lesions were clinically actionable (or requiring follow-up), and 214 (93.9%) were clinically insignificant. Features that differed between patients with clinically insignificant vs. actionable lesions included: age (52.9 ± 15.1 vs. 63.9 ± 15.8 years, p = 0.004), male sex (43.9% vs 71.4%, p = 0.045), history of cirrhosis (6.5% vs 50%, p < 0.001), lesion size (1.9 ± 1.4 cm vs. 3.5 ± 2.8 cm, p = 0.003), heterogeneous lesion echogenicity (16.4% vs. 50%, p = 0.006), and cirrhotic/coarsened background liver (7.5% vs. 35.7%, p = 0.005). Stepwise logistic regression and multivariable analysis identified age, presence of cirrhosis, and lesion size as features most predictive of an actionable lesion (OR 1.04, 24.3, 1.77 respectively). Reader agreement for imaging features was fair to moderate (k = 0.29-0.53). 100%(168/168) of hyperechoic liver lesions measuring ≤ 3 cm in patients without a history of malignancy or underlying liver disease were clinically insignificant. CONCLUSION: Our study findings support the overall favorable diagnoses of hyperechoic liver lesions ≤ 3 cm in patients without underlying risk factors.

Utility of gadolinium for identifying the malignant potential of pancreatic cystic lesions.

PURPOSE: To determine if gadolinium is necessary for the diagnosis of a pancreatic cystic lesion (PCL) as benign or malignant by assessing inter- and intra-observer agreement and diagnostic accuracy for the presence of worrisome features/high-risk stigmata on non-contrast MRI compared to MRI with and without contrast, with cytopathology as a reference standard. METHODS: The institutional database was searched to identify consecutive patients that underwent EUS/FNA or surgical resection of an asymptomatic PCL performed from 01/01/2015 to 01/01/2019. Two abdominal radiologists independently evaluated PCLs on MRI with all sequences except for contrast-enhanced sequences followed by a second reading with data from the entire MRI including pre- and post-contrast sequences. Cyst size, growth, and the presence of worrisome features/high-risk stigmata were assessed for each cyst on both datasets. RESULTS: There were 87 patients with 87 pancreatic cysts; 76(87.4%) were benign and 11 (12.7%) were malignant. The presence of any worrisome features/high-risk stigmata for reader 1 was concordant on both MRIs in 95.4% (83/87; k = 0.874) of cases and for reader 2 was concordant in 96.6% (84/87; k = 0.920) of cases. The diagnostic accuracy of the two datasets when the presence of any worrisome feature/high-risk stigmata was predictive of malignancy was identical for reader 1 (AUC = 0.622 for both; p = 1.0) and similar for reader 2 (AUC 0.569 and 0.589; p = 0.08) for both MRI datasets. CONCLUSION: The addition of gadolinium had no significant impact in the diagnosis of a benign versus malignant PCL, with similar intra-observer agreement and diagnostic accuracy for both readers when using contrast-enhanced and unenhanced MRI datasets.

PI-RADS: what is new and how to use it.

The prostate imaging reporting and data system (PI-RADS) has revolutionized the use of magnetic resonance imaging (MRI) for the management of prostate cancer (PCa). The most recent version 2.1, PI-RADS v2.1, provides specific refinements in the performance, relaxing some recommendations which were not found to be helpful, while reinforcing and clarifying others. The interpretation of T2-weighted imaging (T2WI) in the transition zone (TZ), and the overall assessment of TZ nodules, now allows for a clearer distinction between those which are clearly benign and those which might warrant tissue sampling. Additional changes also resolve discrepancies in T2WI and diffusion-weighted imaging (DWI) of the peripheral zone (PZ). PI-RADS v2.1 is a simpler, more straightforward, and more reproducible method to better communicate between physicians regarding findings on prostate MRI.

Establishing Normal Values for Shear-Wave Elastography of the Renal Cortex in Healthy Adults.

BACKGROUND: Shear-wave elastography of the kidney has emerged as a potential clinical application of this novel imaging tool. However, normal velocity values for shear-wave elastography involving the cortex of healthy kidneys have not been definitively established, and both inter- and intraobserver reliability has yet to be comprehensively evaluated. METHODS: This prospective study involved ultrasound examination of 11 healthy adults. Shear-wave velocity values were obtained at the renal cortex in the longitudinal and transverse planes by both junior (fellow) and senior (attending) radiologists. RESULTS: The mean shear-wave velocity values ranged between 2.82 and 2.9 m/s, which did not vary significantly between observers (junior vs. senior) or method of measurement (longitudinal vs. transverse planes), P = 0.533. However, there was a wide variation for these measurements (0.51-4.99 m/s). Separate analysis of the measurement depth demonstrated no statistically significant association with the shear-wave velocity values, P = 0.477. CONCLUSION: Our results agree with previous publications and help establish normal shear-wave velocity values and their range for the renal cortex in adults.

Multiparametric Quantitative Ultrasound Imaging in Assessment of Chronic Kidney Disease.

OBJECTIVES: To evaluate the value of multiparametric quantitative ultrasound imaging in assessing chronic kidney disease (CKD) using kidney biopsy pathologic findings as reference standards. METHODS: We prospectively measured multiparametric quantitative ultrasound markers with grayscale, spectral Doppler, and acoustic radiation force impulse imaging in 25 patients with CKD before kidney biopsy and 10 healthy volunteers. Based on all pathologic (glomerulosclerosis, interstitial fibrosis/tubular atrophy, arteriosclerosis, and edema) scores, the patients with CKD were classified into mild (no grade 3 and <2 of grade 2) and moderate to severe (at least 2 of grade 2 or 1 of grade 3) CKD groups. Multiparametric quantitative ultrasound parameters included kidney length, cortical thickness, pixel intensity, parenchymal shear wave velocity, intrarenal artery peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index. We tested the difference in quantitative ultrasound parameters among mild CKD, moderate to severe CKD, and healthy controls using analysis of variance, analyzed correlations of quantitative ultrasound parameters with pathologic scores and the estimated glomerular filtration rate (GFR) using Pearson correlation coefficients, and examined the diagnostic performance of quantitative ultrasound parameters in determining moderate CKD and an estimated GFR of less than 60 mL/min/1.73 m2 using receiver operating characteristic curve analysis. RESULTS: There were significant differences in cortical thickness, pixel intensity, PSV, and EDV among the 3 groups (all P < .01). Among quantitative ultrasound parameters, the top areas under the receiver operating characteristic curves for PSV and EDV were 0.88 and 0.97, respectively, for determining pathologic moderate to severe CKD, and 0.76 and 0.86 for estimated GFR of less than 60 mL/min/1.73 m2 . Moderate to good correlations were found for PSV, EDV, and pixel intensity with pathologic scores and estimated GFR. CONCLUSIONS: The PSV, EDV, and pixel intensity are valuable in determining moderate to severe CKD. The value of shear wave velocity in assessing CKD needs further investigation.

Unusual migration of fractured ERCP guidewire: A case report.

Endoscopic retrograde cholangiopancreatography (ERCP) routinely uses hydrophilic guidewires to cannulate ducts and traverse stenoses. Fracture of these guidewires have been reported, however, migration of these fractured fragments is an extremely rare occurrence that has yet to be reported in the literature. We present a case of a fractured ERCP guidewire with extensive migration in the retroperitoneal and lower extremity soft tissues and vasculature with radiologic correlation across multiple modalities-MRI, CT, and radiographs-as well as pathologic correlation. This case illustrates a rare but serious complication of ERCP and demonstrates the imaging findings associated with it.

Association between changes in suspicious prostate lesions on serial MRI examinations and follow-up biopsy results.

We assessed changes in prostate lesions on serial magnetic resonance imaging (MRI) examinations in predicting biopsy results. Fifty-five men undergoing two prostate MRI examinations ≥6 months apart, followed by targeted biopsy, were included. Two radiologists assessed dominant lesions for an increase in size or suspicion score. Progression on MRI had lower sensitivity (23.5%-35.3%) and higher specificity (76.2%-90.5%) than prostate-specific antigen (PSA) velocity (sensitivity 70.6%, specificity 52.4%) for predicting positive biopsy. Highest accuracy was achieved by PSA velocity (63.6%) for positive biopsy, and by MRI (65.5%-72.7%) for Gleason >6 tumor. Findings support lesion progression on MRI serving as a basis for performing subsequent targeted biopsy.

New OPTN/UNOS classification system for nodules in cirrhotic livers detected with MR imaging: effect on hepatocellular carcinoma detection and transplantation allocation.

PURPOSE: To assess the effect of the new Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) policy on hepatocellular carcinoma (HCC) detection and liver transplant allocation in patients with cirrhosis undergoing dynamic contrast material-enhanced liver magnetic resonance (MR) imaging. MATERIALS AND METHODS: In this HIPAA-compliant institutional review board-approved retrospective study with waiver of informed consent, 247 patients (196 men, 51 women; mean age, 60 years ± 11 [standard deviation]) with liver cirrhosis who underwent evaluation for HCC with MR imaging were identified via database search. Three radiologists independently reviewed images and identified number and size of HCC based on criteria within either the prior or revised policy. Based on these interpretations, priority for liver transplantation for each patient was determined with prior and revised transplantation allocation criteria. HCC detection was compared between sessions by using McNemar tests, and interreader agreement for detection of at least one HCC was assessed by using κ coefficients. RESULTS: All three readers detected significantly more 1-2-cm HCCs with the revised policy (readers detected 22, eight, and 20 1-2-cm HCCs) versus the prior policy (no reader detected 1-2-cm HCCs) (P ≤ .031). All readers detected significantly fewer 2-5-cm HCCs with the revised policy (readers detected eight, 13, and 14 2-5-cm HCCs) versus the prior policy (readers detected 24, 21, and 24 2-5-cm HCCs) (P ≤ .027). For all readers, fewer patients met criteria for increased transplantation priority with the revised versus the prior policy (number of patients who received increased priority for the three readers were 4.9% [12 of 247] vs 9.3% [23 of 247]; 5.7% [14 of 247] vs 8.1% [20 of 247]; and 6.9% [17 of 247] vs 8.9% [22 of 247]). Interreader agreement was substantial for the prior policy (κ = 0.607) and almost perfect for the revised policy (κ = 0.813). CONCLUSION: Among cirrhotic patients who underwent evaluation for HCC with MR imaging, the revised OPTN/UNOS policy led to increased detection of 1-2-cm HCCs, decreased detection of 2-5-cm HCCs, and fewer patients who met criteria for increased transplant priority.

Renal masses measuring under 2 cm: pathologic outcomes and associations with MRI features.

PURPOSE: To evaluate pathologic outcomes and associations with MRI features in small renal masses measuring up to 20mm METHODS: 86 patients (61 ± 13 years; 45 M/41F) with 92 renal masses measuring up to 20mm that underwent MRI prior to tissue diagnosis were included. Two radiologists independently evaluated all masses for microscopic lipid, hemorrhage, T2-hyperintensity, T2-homogeneity, cystic/necrotic areas, hypervascularity, enhancement homogeneity, circumscribed margins, and predominantly exophytic location. These MRI features, as well as patient age, gender, and history of RCC, were compared with pathologic findings using Fisher's exact test, unpaired t-test, and multivariate logistic regression. RESULTS: 26.1% (24/92) of masses under 2 cm were benign, only 32.6% (30/92) were clear-cell RCC, and only 7.6% (7/92) were high-grade. Among 16 masses measuring up to 1cm, only 12.5% (2/16) were clear-cell RCC, and none was high-grade. Within the entire cohort, no MRI or clinical feature showed a significant difference between benign and malignant lesions (p ≥ 0.053). However, for both readers, clear-cell RCC exhibited a significantly higher frequency of T2-hyperintensity, cystic/necrotic areas, and hypervascularity, and a significantly lower frequency of hemorrhage, T2-homogeneity, and enhancement homogeneity (p<0.001-0.036). Hypervascularity was a significant independent predictor of clear-cell RCC for both readers (p=0.002-0.007), as was T2-hyperintensity for reader 2 (p=0.007). CONCLUSION: A substantial fraction of small renal masses were benign, and when malignant, largely exhibited indolent pathologic characteristics, particularly when measuring under 1cm Although small benign and malignant masses could not be differentiated on MRI, hypervascularity showed a significant independent association with clear-cell RCC in comparison with other lesions.

CT enterography at 100 kVp with iterative reconstruction compared to 120 kVp filtered back projection: evaluation of image quality and radiation dose in the same patients.

PURPOSE: To perform qualitative and quantitative comparison of images in same patients undergoing CT enterography (CTE) with 100 kVp iterative reconstruction and 120 kVp filtered back projection. METHODS: In this retrospective study, 50 consecutive patients who underwent imaging with 100 kVp and iterative reconstruction (100-IR) and had prior imaging with 120 kVp filtered back projection (120-FBP) were included. Subjective image quality parameters were evaluated by two independent and blinded readers, with higher score implying better image quality. We developed a quantitative measure of image sharpness by measuring edge-width of the psoas-fat interface. Image noise was measured as a standard deviation of attenuation measurement in the homogeneous region of the subcutaneous fat. Image sharpness and noise were measured and compared between 100-IR and 120-FBP acquisitions. RESULTS: There was approximately 33% lower radiation dose as estimated by CTDIvol with 100-IR compared to 120-FBP (9.95 vs. 15.0; p < 0.0001). There were no significant differences in overall image quality, bowel wall sharpness, and subjective assessment of noise and artifact between 100-IR and 120-FBP for both readers. Mesenteric vessel clarity score was significantly higher with 100-IR for 1 reader (4.34 vs. 4.04; p = 0.008), but not for the second reader. There was higher image sharpness (1.62 vs. 1.89; p < 0.0001) and higher image noise (14.4 vs. 13.2; p = 0.020) with 100-IR compared to 120-FBP acquisition. CONCLUSIONS: CTE performed at 100 kVp with iterative reconstruction demonstrates dose reduction without significant impact on various measures of image quality when compared to conventional 120 kVp FBP.

Complex cystic renal masses: comparison of cyst complexity and Bosniak classification between 1.5 T and 3 T MRI.

PURPOSE: To retrospectively compare perceived complexity and Bosniak cyst classification of cystic renal lesions between 1.5 T and 3 T MRI. METHODS: 33 cystic renal lesions in 26 patients that underwent contrast-enhanced MRI at both 1.5 T and 3 T within a 12 month span were included. Two radiologists (R1, R2) independently assessed lesions, unaware of field strength, in terms of number of septations, septal thickening, mural thickening, presence of mural nodule, and Bosniak cyst category. Scores were compared between field strengths for each lesion. RESULTS: R1 observed increases in septal number, septal thickening, mural thickening, and presence of mural nodule at 3T in 8, 7, 4, and 2 lesions, and at 1.5 T in 3, 3, 2, and 0 lesions, respectively; R2 observed increases in septal number, septal thickening, mural thickening, and presence of mural nodule at 3T in 3, 4, 3, and 0 lesions, and at 1.5 T in 2, 0, 0, and 0 lesions, respectively. R1 provided higher Bosniak category at 3T in 9 cases and at 1.5 T in 4 cases; R2 provided higher Bosniak category at 3T in 4 cases and at 1.5 T in 0 cases. Higher scores at 3T than 1.5 T were associated with differences in advised clinical management in 7/9 cases for R1 and 4/4 cases for R2. CONCLUSION: There was an overall tendency for both readers to upgrade cyst complexity and Bosniak cyst category at 3T than 1.5 T, which impacted advised management. Thus, we suggest that serial MRI evaluation of cystic renal lesions be performed at constant field strength.

Impact of size of region-of-interest on differentiation of renal cell carcinoma and renal cysts on multi-phase CT: preliminary findings.

INTRODUCTION: To assess impact of size of regions-of-interest (ROI) on differentiation of RCC and renal cysts using multi-phase CT, with focus on differentiating papillary RCC (pRCC) and cysts given known hypovascularity of pRCC. METHODS: 99 renal lesions (23 pRCC, 47 clear-cell RCC, 7 chromophobe RCC, 22 cysts) underwent multi-phase CT. Subjective presence of visual enhancement was recorded for each lesion. Whole-lesion (WL) ROIs, and small (≤ 5 mm(2)), medium (average size of small and large ROIs), and large (half of lesion diameter) peripherally located partial-lesion (PL) ROIs, were placed on non-contrast and nephrographic phases. Impact of ROI size in separating cysts from all RCC and from pRCC based on increased attenuation between phases was assessed using ROC analysis. RESULTS: Visual enhancement was perceived in 96% of ccRCC, 61% of pRCC, and 9% of cysts. AUCs for separating all RCC and cysts for WL-ROI and small, medium, and large PL-ROIs were 91%, 96%, 91% and 93%, and among lesions without visible enhancement were 60%, 79%, 67% and 67%. AUCs for separating pRCC and cysts for WL-ROI and small, medium, and large PL-ROIs were 78%, 92%, 82% and 84%, and among lesions without visible enhancement were 64%, 88%, 69% and 69%. CONCLUSION: Small PL-ROIs had higher accuracy than WL-ROI or other PL-ROIs in separating RCC from cysts, with greater impact in differentiating pRCC from cysts and differentiating lesions without visible enhancement. Thus, when evaluating renal lesions using multi-phase CT, we suggest placing small peripheral ROIs for highest accuracy in distinguishing renal malignancy and benign cysts.

Utility of MRI features in differentiation of central renal cell carcinoma and renal pelvic urothelial carcinoma.

OBJECTIVE: The purpose of this article is to evaluate the utility of various morphologic and quantitative MRI features in differentiating central renal cell carcinoma (RCC) from renal pelvic urothelial carcinoma. MATERIALS AND METHODS: Sixty patients (39 men and 21 women; mean [± SD] age, 65 ± 14 years; 48 with central RCC and 12 with renal pelvic urothelial carcinoma) who underwent MRI, including diffusion-weighted imaging (b values, 0, 400, and 800 s/mm(2)) and dynamic contrast-enhanced imaging, before histopathologic confirmation were included. Tumor T2 signal intensity and apparent diffusion coefficients (ADCs) were measured and normalized to muscle and CSF (hereafter referred to as normalized T2 signal and normalized ADC, respectively) and then were compared using receiver operating characteristic analysis. Also, two blinded radiologists independently assessed all tumors for various qualitative features, which were compared with the Fisher exact test and unpaired Student t test. RESULTS: Urothelial carcinoma exhibited significantly lower normalized ADC than did RCC (p = 0.008), but no significant difference was seen in ADC or normalized T2 signal intensity (p = 0.247-0.773). Normalized ADC had the highest area under the curve (0.757); normalized ADC below an optimal threshold of 0.451 was associated with sensitivity of 83% and specificity of 71% for diagnosing urothelial carcinoma. Features that were significantly more prevalent in urothelial carcinoma included global impression of urothelial carcinoma, location centered within the collecting system, collecting system defect, extension to the ureteropelvic junction, preserved renal shape, absence of cystic or necrotic areas, absence of hemorrhage, homogeneous enhancement, and hypovascularity (all p < 0.033). Increased T1 signal intensity suggestive of hemorrhage was significantly more prevalent in RCC (p = 0.02). Interreader agreement for the subjective features ranged from 61.7% to 98.3%. CONCLUSION: In addition to various qualitative MRI parameters, normalized ADC has utility in differentiating central RCC from renal pelvic urothelial carcinoma. Such differentiation may assist decisions regarding possible biopsy and treatment planning.

Prevalence, characteristics, and fate of intrahepatic nontumorous arterioportal shunts on MRI in patients with hepatic steatosis.

OBJECTIVE: To assess the frequency, characteristics, and fate of arterioportal shunts in patients with hepatic steatosis and to compare this to the frequency in patients without liver disease. METHODS: Eighty-four patients with hepatic steatosis but no other known liver disease and who underwent 2 abdominal magnetic resonance imaging (MRI) examinations at least 1 year apart formed one study cohort. Eighty-four subjects without steatosis or other known liver disease and who also underwent 2 MRI examinations at least 1 year apart formed a control group. Two radiologists evaluated the initial study for the presence and characteristics of arterial enhancing foci not visible on other sequences and assessed the fate of these foci on the follow-up study. RESULTS: Of the patients with steatosis, 36.9% (95% confidence interval [CI], 26.6%-48.1%) demonstrated a total of 108 arterial enhancing foci, compared with 20 arterial enhancing foci in 13.1% of controls (95% CI, 6.7%-22.2%). Both the number of subjects with at least one arterial enhancing focus and the mean number per subject were significantly greater in the steatosis cohort (P < 0.001). The arterial enhancing foci were generally small and peripheral in location in both cohorts. On follow-up examination, all lesions disappeared, decreased in size, were stable, or increased slightly in size while remaining inconspicuous on other sequences. CONCLUSION: Findings consistent with arterioportal shunts were observed at an unexpectedly high frequency in the control group but at a significantly greater frequency in the steatosis group. All foci exhibited benign behavior on long-term follow-up. Future studies may assess for clinical implications of this finding in patients with hepatic steatosis.

Secondary achalasia and other esophageal motility disorders after laparoscopic Nissen fundoplication for gastroesophageal reflux disease.

OBJECTIVE: The purpose of our investigation was to determine the frequency of secondary achalasia and other esophageal motility disorders revealed on barium studies after laparoscopic Nissen fundoplication and to present the clinical and radiographic findings in these patients. CONCLUSION: Esophageal dysmotility was found in nine (7%) of 138 patients after laparoscopic Nissen fundoplication, including secondary achalasia in three (33%), diffuse esophageal spasm (DES) in two (22%), and a nonspecific esophageal motility disorder in four (44%). Our findings suggest that patients who undergo laparoscopic Nissen fundoplication for gastroesophageal reflux disease are at risk for the development of esophageal motility disorders, including secondary achalasia and DES. Careful evaluation of esophageal motility on postoperative barium studies may help to identify esophageal dysmotility and to differentiate this finding from structural complications of the wrap as a cause of refractory symptoms in these patients.

Age-related structural and functional changes in the breast: multimodality correlation with digital mammography, computed tomography, magnetic resonance imaging, and positron emission tomography.

Preliminary results generated from digital mammography, computed tomography, magnetic resonance imaging, and (18)F-fluorodeoxyglucose positron emission tomography demonstrate concordant findings of decreasing glandular tissue and decreasing metabolic activity with increasing age. These results are presented in the context of a detailed literature review summarizing age-related changes in the breast, both from the histologic/physiologic and the imaging perspectives. We also discuss potential applications of this approach and emphasize the importance of new advanced imaging technologies to offer high levels of quantitative precision for tissue characterization for research and clinical purposes.

Determination of age-related changes in structure and function of skin, adipose tissue, and skeletal muscle with computed tomography, magnetic resonance imaging, and positron emission tomography.

In this article, we report quantitative preliminary data obtained from retrospective analysis of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and combined PET-computed tomography (PET/CT) examinations in subjects ages 3 to 84 years pertaining to changes in the metabolism of skin, subcutaneous adipose tissue, visceral adipose tissue, and skeletal muscle with age, as well as age-related changes in skeletal muscle attenuation. We also propose a new method for identifying hypermetabolic brown fat on FDG-PET. Finally, we present a review of the literature regarding reported age-related structural and functional changes that occur in skin, fat, and skeletal muscle. Using FDG-PET, We evaluated 213 subjects for changes in the metabolism of skin, adipose tissue, and skeletal muscle with aging. Thirty-two separate subjects were chosen to measure maximum standardized uptake value (SUV) of hypermetabolic brown fat on dual-time point PET imaging. Finally, 15 subjects evaluated by PET/CT were selected to measure changes in metabolism and attenuation of skeletal muscle, and changes in metabolism of adipose tissue with aging. We found that skin, fat, and skeletal muscle all demonstrate significant (P < 0.05) increases in SUV with increasing age on PET imaging. Dual-time point PET imaging demonstrates increasing FDG uptake of hypermetabolic brown fat in various regions studied. Finally, our PET/CT studies revealed statistically insignificant (P > 0.05) decreases in SUV of adipose tissue with aging and the opposite trend in skeletal muscles (P > 0.05). Skeletal muscle attenuation in the various regions studied was found to significantly decrease with age (P < 0.05). Our study shows notable trends in metabolism and attenuation of skeletal muscle and metabolism of skin and adipose tissue that occur with normal aging. We hope that the methodologies and data we present here will serve as a useful starting point for those interested in conducting future prospective research on age-related changes in these structures.

Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolism.

We have utilized Caenorhabditis elegans to study human methylmalonic acidemia. Using bioinformatics, a full complement of mammalian homologues for the conversion of propionyl-CoA to succinyl-CoA in the genome of C. elegans, including propionyl-CoA carboxylase subunits A and B (pcca-1, pccb-1), methylmalonic acidemia cobalamin A complementation group (mmaa-1), co(I)balamin adenosyltransferase (mmab-1), MMACHC (cblc-1), methylmalonyl-CoA epimerase (mce-1) and methylmalonyl-CoA mutase (mmcm-1) were identified. To verify predictions that the entire intracellular adenosylcobalamin metabolic pathway existed and was functional, the kinetic properties of the C. elegans mmcm-1 were examined. RNA interference against mmcm-1, mmab-1, mmaa-1 in the presence of propionic acid revealed a chemical phenotype of increased methylmalonic acid; deletion mutants of mmcm-1, mmab-1 and mce-1 displayed reduced 1-[(14)C]-propionate incorporation into macromolecules. The mutants produced increased amounts of methylmalonic acid in the culture medium, proving that a functional block in the pathway caused metabolite accumulation. Lentiviral delivery of the C. elegans mmcm-1 into fibroblasts derived from a patient with mut(o) class methylmalonic acidemia could partially restore propionate flux. The C. elegans mce-1 deletion mutant demonstrates for the first time that a lesion at the epimerase step of methylmalonyl-CoA metabolism can functionally impair flux through the methylmalonyl-CoA mutase pathway and suggests that malfunction of MCEE may cause methylmalonic acidemia in humans. The C. elegans system we describe represents the first lower metazoan model organism of mammalian propionate spectrum disorders and demonstrates that mass spectrometry can be employed to study a small molecule chemical phenotype in C. elegans RNAi and deletion mutants.