Magnetization Transfer MRI Contrast May Correlate with Tissue Redox State in Prostate Cancer.

Developing imaging biomarkers for non-invasive measurement of the tissue redox state is a key research area. Recently, we presented the first non-invasive MR imaging method that demonstrated the correlation between the endogenous chemical exchange saturation transfer (CEST) contrast and the tissue redox state. It is well known that the broadband magnetization transfer (MT) can occur via chemical exchange (CEST) and/or dipole-dipole interactions. The present study investigated if the broadband MT also correlated with the tissue redox state. The preliminary result for the prostate tumor xenografts indeed showed a significant correlation between the broadband MT contrast and the NADH redox ratio quantified with the optical redox scanning. In vivo MT contrast, once calibrated, may potentially serve as an imaging biomarker for tissue redox state.

The feasibility of quantitative MRI of perivascular spaces at 7T.

BACKGROUND: Dilated brain perivascular spaces (PVSs) are found to be associated with many conditions, including aging, dementia, and Alzheimer's disease (AD). Conventionally, PVS assessment is mainly based on subjective observations of the number, size and shape of PVSs in MR images collected at clinical field strengths (≤3T). This study tests the feasibility of imaging and quantifying brain PVS with an ultra-high 7T whole-body MRI scanner. NEW METHOD: 3D high resolution T2-weighted brain images from healthy subjects (n=3) and AD patients (n=5) were acquired on a 7T whole-body MRI scanner. To automatically segment the small hyperintensive fluid-filling PVS structures, we also developed a quantitative program based on algorithms for spatial gradient, component connectivity, edge-detection, k-means clustering, etc., producing quantitative results of white matter PVS volume densities. RESULTS: The 3D maps of automatically segmented PVS show an apparent increase in PVS density in AD patients compared to age-matched healthy controls due to the PVS dilation (8.0±2.1 v/v% in AD vs. 4.9±1.3 v/v% in controls, p<0.05). COMPARISON WITH EXISTING METHOD: We demonstrated that 7T provides sufficient SNR and resolution for quantitatively measuring PVSs in deep white matter that is challenging with clinical MRI systems (≤3T). Compared to the conventional visual counting and rating for the PVS assessment, the quantitation method we developed is automatic and objective. CONCLUSIONS: Quantitative PVS MRI at 7T may serve as a non-invasive and endogenous imaging biomarker for diseases with PVS dilation.

CEST signal at 2ppm (CEST@2ppm) from Z-spectral fitting correlates with creatine distribution in brain tumor.

In general, multiple components such as water direct saturation, magnetization transfer (MT), chemical exchange saturation transfer (CEST) and aliphatic nuclear Overhauser effect (NOE) contribute to the Z-spectrum. The conventional CEST quantification method based on asymmetrical analysis may lead to quantification errors due to the semi-solid MT asymmetry and the aliphatic NOE located on a single side of the Z-spectrum. Fitting individual contributors to the Z-spectrum may improve the quantification of each component. In this study, we aim to characterize the multiple exchangeable components from an intracranial tumor model using a simplified Z-spectral fitting method. In this method, the Z-spectrum acquired at low saturation RF amplitude (50 Hz) was modeled as the summation of five Lorentzian functions that correspond to NOE, MT effect, bulk water, amide proton transfer (APT) effect and a CEST peak located at +2 ppm, called CEST@2ppm. With the pixel-wise fitting, the regional variations of these five components in the brain tumor and the normal brain tissue were quantified and summarized. Increased APT effect, decreased NOE and reduced CEST@2ppm were observed in the brain tumor compared with the normal brain tissue. Additionally, CEST@2ppm decreased with tumor progression. CEST@2ppm was found to correlate with the creatine concentration quantified with proton MRS. Based on the correlation curve, the creatine contribution to CEST@2ppm was quantified. The CEST@2ppm signal could be a novel imaging surrogate for in vivo creatine, the important bioenergetics marker. Given its noninvasive nature, this CEST MRI method may have broad applications in cancer bioenergetics.

Development of superficial white matter and its structural interplay with cortical gray matter in children and adolescents.

Healthy human brain undergoes significant changes during development. The developmental trajectory of superficial white matter (SWM) is less understood relative to cortical gray matter (GM) and deep white matter. In this study, a multimodal imaging strategy was applied to vertexwise map SWM microstructure and cortical thickness to characterize their developmental pattern and elucidate SWM-GM associations in children and adolescents. Microscopic changes in SWM were evaluated with water diffusion parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in 133 healthy subjects aged 10-18 years. Results demonstrated distinct maturational patterns in SWM and GM. SWM showed increasing FA and decreasing MD and RD underneath bilateral motor sensory cortices and superior temporal auditory cortex, suggesting increasing myelination. A second developmental pattern in SWM was increasing FA and AD in bilateral orbitofrontal regions and insula, suggesting improved axonal coherence. These SWM patterns diverge from the more widespread GM maturation, suggesting that cortical thickness changes in adolescence are not explained by the encroachment of SWM myelin into the GM-WM boundary. Interestingly, age-independent intrinsic association between SWM and cortical GM seems to follow functional organization of polymodal and unimodal brain regions. Unimodal sensory areas showed positive correlation between GM thickness and FA whereas polymodal regions showed negative correlation. Axonal coherence and differences in interstitial neuron composition between unimodal and polymodal regions may account for these SWM-GM association patterns. Intrinsic SWM-GM relationships unveiled by neuroimaging in vivo can be useful for examining psychiatric disorders with known WM/GM disturbances.