The assessment of vascular anatomy and functions using magnetic resonance imaging (MRI) is critical for medical diagnosis, whereas the commonly used low‐field MRI system (≤3 T) suffers from low spatial resolution. Ultrahigh field (UHF) MRI (≥7 T), with significantly improved resolution and signal‐to‐noise ratio, shows great potential to provide high‐resolution vasculature images. However, practical applications of UHF MRI technology for vascular imaging are currently limited by the low sensitivity and accuracy of single‐mode (T1 or T2) contrast agents. Herein, a UHF‐tailored T1–T2 dual‐mode iron oxide nanoparticle‐based contrast agent (UDIOC) with extremely small core size and ultracompact hydrophilic surface modification, exhibiting dually enhanced T1–T2 contrast effect under the 7 T magnetic field, is reported. The UDIOC enables clear visualization of microvasculature as small as ≈140 µm in diameter under UHF MRI, extending the detection limit of the 7 T MR angiography. Moreover, by virtue of high‐resolution UHF MRI and a simple double‐checking process, UDIOC‐based dual‐mode dynamic contrast‐enhanced MRI is successfully applied to detect tumor vascular permeability with extremely high sensitivity and accuracy, providing a novel paradigm for the precise medical diagnosis of vascular‐related diseases.
BackgroundThe shutter‐speed model dynamic contrast‐enhanced (SSM‐DCE) MRI pharmacokinetic analysis adds a metabolic dimension to DCE‐MRI. This is of particular interest in cancers, since abnormal metabolic activity might happen.PurposeTo develop a DCE‐MRI SSM analysis framework for glioblastoma multiforme (GBM) cases considering the heterogeneous tissue found in GBM.Study TypeProspective.SubjectsTen GBM patients.Field Strength/Sequence3T MRI with DCE‐MRI.AssessmentsThe corrected Akaike information criterion (AICc) was used to automatically separate DCE‐MRI data into proper SSM versions based on the contrast agent (CA) extravasation in each pixel. The supra‐intensive parameters, including the vascular water efflux rate constant (kbo), the cellular efflux rate constant (kio), and the CA vascular efflux rate constant (kpe), together with intravascular and extravascular–extracellular water mole fractions (pb and po, respectively) were determined. Further error analyses were also performed to eliminate unreliable estimations on kio and kbo.Statistical TestsStudent's t‐test.ResultsFor tumor pixels of all subjects, 88% show lower AICc with SSM than with the Tofts model. Compared to normal‐appearing white matter (NAWM), tumor tissue showed significantly larger pb (0.045 vs. 0.011, P < 0.001) and higher kpe (3.0 × 10−2 s−1 vs. 6.1 × 10−4 s−1, P < 0.001). In the contrast, significant kbo reduction was observed from NAWM to GBM tumor tissue (2.8 s−1 vs. 1.0 s−1, P < 0.001). In addition, kbo is four orders and two orders of magnitude greater than kpe in the NAWM and GBM tumor, respectively. These results indicate that CA and water molecule have different transmembrane pathways. The mean tumor kio of all subjects was 0.57 s−1.Data ConclusionWe demonstrate the feasibility of applying SSM models in GBM cases. Within the proposed SSM analysis framework, kio and kbo could be estimated, which might be useful biomarkers for GBM diagnosis and survival prediction in future.Level of Evidence4Technical EfficacyStage 1 J. Magn. Reson. Imaging 2020;52:850–863.
Mounting evidence supports that oligodendrocyte precursor cells (OPCs) play important roles in maintaining the integrity of normal brains, and that their dysfunction is the etiology of numerous severe neurological diseases. OPCs exhibit diverse heterogeneity in the adult brain, and distinct germinal zones of the embryonic brain contribute to OPC genesis. However, it remains obscure whether developmental origins shape OPC heterogeneity in the adult brain.Here, an in vivo clonal analysis approach is developed to address this. By combining OPC-specific transgenes, in utero electroporation, and the PiggyBac transposon system, the lineages of individual neonatal OPCs derived from either dorsal or ventral embryonic germinal zones are traced, and the landscape of their trajectories is comprehensively described throughout development. Surprisingly, despite behaving indistinguishably in the brain before weaning, dorsally derived OPCs continuously expand throughout life, but ventrally derived OPCs eventually diminish. Importantly, clonal analysis supports the existence of an intrinsic cellular "clock" to control OPC expansion. Moreover, knockout of NF1 could circumvent the distinction of ventrally derived OPCs in the adult brain. Together, this work shows the importance of in vivo clonal analysis in studying stem/progenitor cell heterogeneity, and reveals that developmental origins play a role in determining OPC fate.
Ischemic lesions could lead to secondary degeneration in remote regions of the brain. However, the spatial distribution of secondary degeneration along with its role in functional deficits is not well understood. In this study, we explored the spatial and connectivity properties of white matter (WM) secondary degeneration in a focal unilateral sensorimotor cortical ischemia rat model, using advanced microstructure imaging on a 14 T MRI system. Significant axonal degeneration was observed in the ipsilateral external capsule and even remote regions including the contralesional external capsule and corpus callosum. Further fiber tractography analysis revealed that only fibers having direct axonal connections with the primary lesion exhibited a significant degeneration. These results suggest that focal ischemic lesions may induce remote WM degeneration, but limited to fibers tied to the primary lesion. These “direct” fibers mainly represent perilesional, interhemispheric, and subcortical axonal connections. At last, we found that primary lesion volume might be the determining factor of motor function deficits.
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