Zhen J. Wang

Dual-Energy and Low-kVp CT in the Abdomen

OBJECTIVE The purpose of this article is to discuss the influence of tube potential on CT images and explore the potential impact of dual-energy CT on imaging of the abdomen and pelvis. CONCLUSION Low peak tube voltage (kVp) settings provide high conspicuity of contrast materials at CT but may result in high image noise, particularly in larger patients. Material decomposition at dual-energy CT can differentiate renal stones by their composition, quantify tissue iron stores, improve the detection of pathologic hyperenhancement, and reduce contrast material and radiation dose compared with conventional CT. Further clinical research and technique refinement will be needed as the usage of these exciting technologies spreads.

Aromatase (Cyp19) expression is up-regulated by targeted disruption of Dax1

DAX-1 [dosage-sensitive sex reversal, adrenal hypoplasia congenita (AHC) critical region on the X chromosome, gene 1] is an orphan nuclear receptor that represses transcription by steroidogenic factor-1 (SF-1), a factor that regulates expression of multiple steroidogenic enzymes and other genes involved in reproduction. Mutations in the human DAX1 gene (also known as AHC) cause the X-linked syndrome AHC, a disorder that is associated with hypogonadotropic hypogonadism also. Characterization of Dax1-deficient male mice revealed primary testicular defects that included Leydig cell hyperplasia (LCH) and progressive degeneration of the germinal epithelium, leading to infertility. In this study, we investigated the effect of Dax1 disruption on the expression profile of various steroidogenic enzyme genes in Leydig cells isolated from Dax1-deficient male mice. Expression of the aromatase (Cyp19) gene, which encodes the enzyme that converts testosterone to estradiol, was increased significantly in the Leydig cells isolated from mutant mice, whereas the expression of other proteins (e.g., StAR and Cyp11a) was not altered. In in vitro transfection studies, DAX-1 repressed the SF-1-mediated transactivation of the Cyp19 promoter but did not inhibit the StAR or Cyp11a promoters. Elevated Cyp19 expression was accompanied by increased intratesticular levels of estradiol. Administration of tamoxifen, a selective estrogen-receptor modulator, restored fertility to the Dax1-deficient male mice and partially corrected LCH, suggesting that estrogen excess contributes to LCH and infertility. Based on these in vivo and in vitro analyses, aromatase seems to be a physiologic target of Dax-1 in Leydig cells, and increased Cyp19 expression may account, in part, for the infertility and LCH in Dax1-deficient mice.

Hyperpolarized 13C-pyruvate magnetic resonance reveals rapid lactate export in metastatic renal cell carcinomas

Renal cell carcinomas (RCC) are a heterogeneous group of tumors with a wide range of aggressiveness. Noninvasive methods to confidently predict the tumor biologic behavior and select appropriate treatment are lacking. Here, we investigate the dynamic metabolic flux in living RCC cells using hyperpolarized (13)C-pyruvate magnetic resonance spectroscopy (MRS) combined with a bioreactor platform and interrogated the biochemical basis of the MRS data with respect to cancer aggressiveness. RCC cells have significantly higher pyruvate-to-lactate flux than the normal renal tubule cells. Furthermore, a key feature distinguishing the localized from the metastatic RCC cells is the lactate efflux rate, mediated by the monocarboxylate transporter 4 (MCT4). The metastatic RCC cells have significantly higher MCT4 expression and corresponding higher lactate efflux, which is essential for maintaining a high rate of glycolysis. We show that such differential cellular transporter expression and associated metabolic phenotype can be noninvasively assessed via real-time monitoring of hyperpolarized (13)C-pyruvate-to-lactate flux.

Metabolic Reprogramming and Validation of Hyperpolarized 13C Lactate as a Prostate Cancer Biomarker Using a Human Prostate Tissue Slice Culture Bioreactor

The treatment of prostate cancer has been impeded by the lack of both clinically relevant disease models and metabolic markers that track tumor progression. Hyperpolarized (HP) 13C MR spectroscopy has emerged as a new technology to investigate the metabolic shifts in prostate cancer. In this study, we investigate the glucose reprogramming using HP 13C pyruvate MR in a patient‐derived prostate tissue slice culture (TSC) model.

Renal cyst pseudoenhancement at multidetector CT: What are the effects of number of detectors and peak tube voltage?

PURPOSE To determine the effect of the number of detectors and peak tube voltage on renal cyst pseudoenhancement in a phantom model. MATERIALS AND METHODS This study on computed tomographic (CT) phantoms did not require institutional review board approval. The renal compartments of a CT phantom were filled with iodinated contrast material diluted to attain attenuations of 40, 140, and 240 HU. Saline-filled cylinders simulating cysts of varying diameters (range, 0.7-3.0 cm) were serially suspended in the renal compartments and scanned at 80, 90, 100, 120, and 140 kVp in 16-detector (n = 3) and 64-detector (n = 2) CT scanners. Generalized estimating equations were used to determine predictors of cyst pseudoenhancement (defined as a >10 HU increase in cyst attenuation when the background renal attenuation increased from 40 to 140 or 240 HU). RESULTS Pseudoenhancement was seen with higher frequency (59 [61%] of 96 cysts vs 52 [39%] of 132 cysts, P < .05) and magnitude (17 vs 13 HU, P < .005) with 64- rather than with 16-detector scanners. Pseudoenhancement was also seen with higher frequency (25 [42%] of 60 cysts vs 11 [18%] of 60 cysts, P < .005) and magnitude (18 vs 13 HU, P < .05) at 140 kVp than at 80 or 90 kVp. Cyst pseudoenhancement increased with higher background renal enhancement (P < .005) and smaller cyst diameter (P < .05). The number of detectors, peak tube voltage, renal parenchymal enhancement level, and cyst diameter were independent predictors of cyst pseudoenhancement. CONCLUSION Lower tube voltage settings may be useful when accurate differentiation between small renal cysts and solid masses is critical, particularly for 64-detector CT scanners.

Fetal tracheolaryngeal airway obstruction: prenatal evaluation by sonography and MRI.

We reviewed the sonographic and MRI findings of tracheolaryngeal obstruction in the fetus. Conditions that can cause tracheolaryngeal obstruction include extrinsic causes such as lymphatic malformation, cervical teratoma and vascular rings and intrinsic causes such as congenital high airway obstruction syndrome (CHAOS). Accurate distinction of these conditions by sonography or MRI can help facilitate parental counseling and management, including the decision to utilize the ex utero intrapartum treatment (EXIT) procedure.

Assessment of renal fibrosis in chronic kidney disease using diffusion-weighted MRI

AIM To assess the performance of diffusion-weighted magnetic resonance imaging (MRI) for the assessment of renal fibrosis in chronic kidney disease (CKD), with histopathology as a reference standard. MATERIALS AND METHODS Forty patients with CKD and 30 healthy volunteers were recruited for the study. All participants underwent diffusion-weighted MRI. Renal biopsy was performed in 25 patients with CKD. Mean renal medullary and cortical apparent diffusion coefficient (ADC) values were compared between CKD patients and the healthy volunteers. Pearsons correlation coefficient was calculated to investigate the relationship between ADC values, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), 24 h urinary protein (24h-UPRO), and renal histopathological scores. RESULTS Cortical and medullary ADC values in the CKD group were significantly lower compared to those in the healthy controls. In the CKD group, a significant negative correlation was found between cortical ADC values and SCr/24h-UPRO, and significant positive correlation was found between cortical ADC and eGFR. There was also a significant negative correlation between medullary ADC values and SCr. Both cortical and medullary ADC values were significantly correlated with histopathological fibrosis score. CONCLUSION Renal ADC values strongly correlate with histological measures of fibrosis, and have the potential to enhance the non-invasive monitoring of chronic kidney disease.

Hyperpolarized [1-13C]Dehydroascorbate MR Spectroscopy in a Murine Model of Prostate Cancer: Comparison with 18F-FDG PET

Reduction and oxidation (redox) chemistry is increasingly implicated in cancer pathogenesis. To interrogate the redox status of prostate tumors noninvasively, we developed hyperpolarized [1-13C]dehydroascorbate (13C-DHA), the oxidized form of vitamin C, as an MR probe. In a model of transgenic adenocarcinoma of the mouse prostate (TRAMP), increased reduction of hyperpolarized 13C-DHA to vitamin C was observed in tumor, as compared with normal prostate and surrounding benign tissue. We hypothesized that this difference was due to higher concentrations of glutathione and increased transport of hyperpolarized 13C-DHA via the glucose transporters (GLUT1, GLUT3, and GLUT4) in TRAMP tumor. To test these hypotheses, hyperpolarized 13C-DHA MR spectroscopy (MRS) and 18F-FDG PET were applied as complementary technologies in the TRAMP model. Methods: Late-stage TRAMP tumors (>4 cm3) were studied at similar time points (MR studies conducted < 24 h after PET) in fasting mice by 18F-FDG PET and hyperpolarized 13C-DHA MR imaging on a small-animal PET/CT scanner and a 1H/3C 3-T MR scanner. PET data were processed using open-source AMIDE software to compare the standardized uptake values of tumor with those of surrounding muscle, and 13C-DHA MRS data were processed using custom software to compare the metabolite ratios (vitamin C/[vitamin C + 13C-DHA]). After in vivo studies, the tumor glutathione concentrations were determined using a spectrophotometric assay, and thiol staining was performed using mercury orange. Real-time polymerase chain reaction was used to evaluate the relevant transporters GLUT1, GLUT3, and GLUT4 and vitamin C transporters SVCT1 and SVCT2. GLUT1 was also evaluated by immunohistochemistry. Results: The average metabolite ratio was 0.28 ± 0.02 in TRAMP tumor, versus 0.11 ± 0.02 in surrounding benign tissue (n = 4), representing a 2.5-fold difference. The corresponding tumor-to-nontumor 18F-FDG uptake ratio was 3.0. The total glutathione was 5.1 ± 0.4 mM in tumor and 1.0 ± 0.2 mM in normal prostate, whereas reduced glutathione was 2.0 ± 0.3 mM and 0.8 ± 0.3 mM, respectively, corresponding to a 2.5-fold difference. In TRAMP tumor, mercury orange staining demonstrated increased thiols. Real-time polymerase chain reaction showed no significant difference in GLUT1 messenger RNA between TRAMP tumor and normal prostate, with immunohistochemistry (anti-GLUT1) also showing comparable staining. Conclusion: Both hyperpolarized 13C-DHA and 18F-FDG provide similar tumor contrast in the TRAMP model. Our findings suggest that the mechanism of in vivo hyperpolarized 13C-DHA reduction and the resulting tumor contrast correlates most strongly with glutathione concentration. In the TRAMP model, GLUT1 is not significantly upregulated and is unlikely to account for the contrast obtained using hyperpolarized 13C-DHA or 18F-FDG.

Radiologic mimics of cirrhosis.

OBJECTIVE The objective of this article is to provide a practical review of the conditions other than cirrhosis that can result in diffuse surface nodularity of the liver or portal hypertension. CONCLUSION Conditions that can mimic cirrhosis on imaging include pseudocirrhosis of treated breast cancer metastases to the liver, fulminant hepatic failure, miliary metastases, sarcoidosis, schistosomiasis, congenital hepatic fibrosis, idiopathic portal hypertension, early primary biliary cirrhosis, chronic Budd-Chiari syndrome, chronic portal vein thrombosis, and nodular regenerative hyperplasia.

Blood oxygen level-dependent (BOLD) MRI of diabetic nephropathy: Preliminary experience

To evaluate the blood oxygen level‐dependent (BOLD) magnetic resonance imaging (MRI) findings in kidneys of patients with diabetic nephropathy.