Assessing Cerebral Oxygen Metabolism Changes in Patients With Preeclampsia Using Voxel-Based Morphometry of Oxygen Extraction Fraction Maps in Magnetic Resonance Imaging.

OBJECTIVE: The objective of this study was to analyze the different brain oxygen metabolism statuses in preeclampsia using magnetic resonance imaging and investigate the factors that affect cerebral oxygen metabolism in preeclampsia. MATERIALS AND METHODS: Forty-nine women with preeclampsia (mean age 32.4 years; range, 18-44 years), 22 pregnant healthy controls (PHCs) (mean age 30.7 years; range, 23-40 years), and 40 non-pregnant healthy controls (NPHCs) (mean age 32.5 years; range, 20-42 years) were included in this study. Brain oxygen extraction fraction (OEF) values were computed using quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level-dependent magnitude-based OEF mapping (QSM + quantitative blood oxygen level-dependent imaging or QQ) obtained with a 1.5-T scanner. Voxel-based morphometry (VBM) was used to investigate the differences in OEF values in the brain regions among the groups. RESULTS: Among the three groups, the average OEF values were significantly different in multiple brain areas, including the parahippocampus, multiple gyri of the frontal lobe, calcarine, cuneus, and precuneus (all P-values were less than 0.05, after correcting for multiple comparisons). The average OEF values of the preeclampsia group were higher than those of the PHC and NPHC groups. The bilateral superior frontal gyrus/bilateral medial superior frontal gyrus had the largest size of the aforementioned brain regions, and the OEF values in this area were 24.2 ± 4.6, 21.3 ± 2.4, and 20.6 ± 2.8 in the preeclampsia, PHC, and NPHC groups, respectively. In addition, the OEF values showed no significant differences between NPHC and PHC. Correlation analysis revealed that the OEF values of some brain regions (mainly involving the frontal, occipital, and temporal gyrus) were positively correlated with age, gestational week, body mass index, and mean blood pressure in the preeclampsia group (r = 0.361-0.812). CONCLUSION: Using whole-brain VBM analysis, we found that patients with preeclampsia had higher OEF values than controls.

Carbonic anhydrase IX stratifies patient prognosis and identifies nodal status in animal models of nasopharyngeal carcinoma using a targeted imaging strategy.

PURPOSE: Accurate identification of nodal status enables adequate neck irradiation for nasopharyngeal carcinoma (NPC). However, most conventional techniques are unable to pick up occult metastases, leading to underestimation of tumor extensions. Here we investigate the clinical significance of carbonic anhydrase IX (CAIX) in human NPC samples, and develop a CAIX-targeted imaging strategy to identify occult lymph node metastases (LNMs) and extranodal extension (ENE) in animal studies. METHODS: A total of 211 NPC samples are performed CAIX staining, and clinical outcomes are analyzed. The metastatic murine models are generated by foot pad injection of NPC cells, and a CAIX-targeted imaging agent (CAIX-800) is intravenously administered. We adopt fluorescence molecular tomography and ultrasonography (US)-guided spectroscopic photoacoustic (sPA) imaging to perform in vivo studies. Histological and immunohistochemical characterization are carried out via node-by-node analysis. RESULTS: For clinical samples, 90.1% (91/101) primary tumors, 73.3% (66/90) metastases, and 100% (20/20) local recurrences are CAIX positive. In metastases group, 84.7% (61/72) nodal metastases and 22.2% (4/18) organ metastases are CAIX positive. CAIX expression in primary tumors is significantly associated with NPC stage and prognosis. For animal studies, CAIX-800-based fluorescence imaging achieves 81.3% sensitivity and 93.8% specificity in detecting occult LNMs in vivo, with a minimum detectable diameter of 1.7 mm. Coupled with CAIX-800, US-guided sPA imaging could not only detect subcapsular deposits of metastatic cancer cells 2 weeks earlier than conventional techniques, but also successfully track pathological ENE. CONCLUSION: CAIX remarkably expresses in human NPCs and stratifies patient prognosis. In preclinical studies, CAIX-800-based imaging successfully identifies occult LNMs and tracks early stage of pathological ENE. This attractive method shows potential in clinic, allowing medical workers to longitudinally monitor nodal status and helping to reduce unnecessary nodal biopsy for patients with NPC. The schematic diagram for the study. CAIX, carbonic anhydrase IX; NPC, nasopharyngeal carcinoma; US, ultrasonography; sPA, spectroscopic photoacoustic.

Validation of MRI quantitative susceptibility mapping of superparamagnetic iron oxide nanoparticles for hyperthermia applications in live subjects.

The use of magnetic fluid hyperthermia (MFH) for cancer therapy has shown promise but lacks suitable methods for quantifying exogenous irons such as superparamagnetic iron oxide (SPIO) nanoparticles as a source of heat generation under an alternating magnetic field (AMF). Application of quantitative susceptibility mapping (QSM) technique to prediction of SPIO in preclinical models has been challenging due to a large variation of susceptibility values, chemical shift from tissue fat, and noisier data arising from the higher resolution required to visualize the anatomy of small animals. In this study, we developed a robust QSM for the SPIO ferumoxytol in live mice to examine its potential application in MFH for cancer therapy. We demonstrated that QSM was able to simultaneously detect high level ferumoxytol accumulation in the liver and low level localization near the periphery of tumors. Detection of ferumoxytol distribution in the body by QSM, however, required imaging prior to and post ferumoxytol injection to discriminate exogenous iron susceptibility from other endogenous sources. Intratumoral injection of ferumoxytol combined with AMF produced a ferumoxytol-dose dependent tumor killing. Histology of tumor sections corroborated QSM visualization of ferumoxytol distribution near the tumor periphery, and confirmed the spatial correlation of cell death with ferumoxytol distribution. Due to the dissipation of SPIOs from the injection site, quantitative mapping of SPIO distribution will aid in estimating a change in temperature in tissues, thereby maximizing MFH effects on tumors and minimizing side-effects by avoiding unwanted tissue heating.

Evaluation of diffusion kurtosis imaging in stratification of nonalcoholic fatty liver disease and early diagnosis of nonalcoholic steatohepatitis in a rabbit model.

PURPOSE: To examine the feasibility of MR diffusion kurtosis imaging (DKI) for characterizing nonalcoholic fatty liver disease (NAFLD) and diagnosing nonalcoholic steatohepatitis (NASH). METHODS: Thirty-two rabbits on high fat diet with different severities of NAFLD were imaged at 3 T MR including diffusion weighted imaging (DWI) and DKI using b values of 0, 400, 800 s/mm2 with 15 diffusion directions at each b value. Apparent diffusion coefficient (ADC) was derived from the linear exponential DWI model. Mean diffusion (MD) and mean kurtosis (MK) were derived from the quadratic exponential model of DKI. Correlations between MR parameters and hepatic pathology determined by the NAFLD activity scoring system were analyzed by Spearman rank correlation analysis. Receiver operating characteristic analyses were applied to determine the cutoff values of MD, MK as well as ADC in distinguishing NASH from non-NASH. The diagnostic efficacies of MD and MK in detecting NASH were compared with that of ADC. RESULTS: Values for ADC and MD significantly decreased as the severity of NAFLD increased (ρ = -0.529, -0.904, respectively; P < 0.05). MK values significantly increased as the severity of NAFLD increased (ρ = 0.761; P < 0.05). In addition, both MD and MK values were significantly different between borderline NASH and NASH groups (MD: 1.729 ±â€¯0.144 vs. 1.458 ±â€¯0.240[×10-3 mm2/s]; MK: 1.096 ±â€¯0.079 vs. 1.237 ±â€¯0.180; P < 0.05). Moreover, there was a significantly higher area under the curve (AUC) for both MD (0.955) and MK (0.905), as compared to ADC (0.736). CONCLUSION: Diffusion kurtosis imaging was feasible for stratifying NAFLD, and more accurately discriminated NASH from non-NASH when compared with DWI.