Faculty Bibliography

BACKGROUND AND PURPOSE/OBJECTIVE:Multiple Sclerosis (MS) is a progressive, inflammatory, neuro-degenerative disease of the central nervous system (CNS) characterized by a wide range of histopathological features including vascular abnormalities. In this study, an ultra-small superparamagnetic iron oxide (USPIO) contrast agent, Ferumoxytol, was administered to induce an increase in susceptibility for both arteries and veins to help better reveal the cerebral microvasculature. The purpose of this work was to examine the presence of vascular abnormalities and vascular density in MS lesions using high-resolution susceptibility weighted imaging (SWI). METHODS:Six subjects with relapsing remitting MS (RRMS, age = 47.3 ± 11.8 years with 3 females and 3 males) and fourteen age-matched healthy controls were scanned at 3 T with SWI acquired before and after the infusion of Ferumoxytol. Composite data was generated by registering the FLAIR data to the high resolution SWI data in order to highlight the vascular information in MS lesions. Both the central vein sign (CVS) and, a new measure, the multiple vessel sign (MVS) were identified, along with any vascular abnormalities, in the lesions on pre- and post-contrast SWI-FLAIR fusion data. The small vessel density within the periventricular normal-appearing white matter (NAWM) and the periventricular lesions were compared for all subjects. RESULTS:Averaged across two independent raters, a total of 530 lesions were identified across all patients. The total number of lesions with vascularity on pre- and post-contrast data were 287 and 488, respectively. The lesions with abnormal vascular behavior were broken up into following categories: small lesions appearing only at the vessel boundary; dilated vessels within the lesions; and developmental venous angiomas. These vessel abnormalities observed within lesions increased from 55 on pre-contrast data to 153 on post-contrast data. Finally, across all the patients, the periventricular lesional vessel density was significantly higher (p < 0.05) than that of the periventricular NAWM. CONCLUSIONS:By inducing a super-paramagnetic susceptibility in the blood using Ferumoxytol, the vascular abnormalities in the RRMS patients were revealed and small vessel densities were obtained. This approach has the potential to monitor the venous vasculature present in MS lesions, catalogue their characteristics and compare the vascular structures spatially to the presence of lesions. These enhanced vascular features may provide new insight into the pathophysiology of MS.

There is an urgent need for better detection and understanding of vascular abnormalities at the micro-level, where critical vascular nourishment and cellular metabolic changes occur. This is especially the case for structures such as the midbrain where both the feeding and draining vessels are quite small. Being able to monitor and diagnose vascular changes earlier will aid in better understanding the etiology of the disease and in the development of therapeutics. In this work, thirteen healthy volunteers were scanned with a dual echo susceptibility weighted imaging (SWI) sequence, with a resolution of 0.22 ​× ​0.44 ​× ​1 ​mm³ at 3T. Ultra-small superparamagnetic iron oxides (USPIO) were used to induce an increase in susceptibility in both arteries and veins. Although the increased vascular susceptibility enhances the visibility of small subvoxel vessels, the accompanying strong signal loss of the large vessels deteriorates the local tissue contrast. To overcome this problem, the SWI data were acquired at different time points during a gradual administration (final concentration ​= ​4 ​mg/kg) of the USPIO agent, Ferumoxytol, and the data was processed to combine the SWI data dynamically, in order to see through these blooming artifacts. The major vessels and their tributaries (such as the collicular artery, peduncular artery, peduncular vein and the lateral mesencephalic vein) were identified on the combined SWI data using arterio-venous maps. Dynamically combined SWI data was then compared with previous histological work to validate that this protocol was able to detect small vessels on the order of 50 ​μm-100 ​μm. A complex division-based phase unwrapping was also employed to improve the quality of quantitative susceptibility maps by reducing the artifacts due to aliased voxels at the vessel boundaries. The smallest detectable vessel size was then evaluated by revisiting numerical simulations, using estimated true susceptibilities for the basal vein and the posterior cerebral artery in the presence of Ferumoxytol. These simulations suggest that vessels as small as 50 ​μm should be visible with the maximum dose of 4 ​mg/kg.

Imaging brain microvasculature is important in cerebrovascular diseases. However, there is still a lack of non-invasive, non-radiation, and whole-body imaging techniques to investigate them. The aim of this study is to develop an ultra-small superparamagnetic iron oxide (USPIO) enhanced susceptibility weighted imaging (SWI) method for imaging micro-vasculature in both animal (~10 μm in rat) and human brain. We hypothesized that the USPIO-SWI technique could improve the detection sensitivity of the diameter of small subpixel vessels 10-fold compared with conventional MRI methods. Computer simulations were first performed with a double-cylinder digital model to investigate the theoretical basis for this hypothesis. The theoretical results were verified using in vitro phantom studies and in vivo rat MRI studies (n = 6) with corresponding ex vivo histological examinations. Additionally, in vivo human studies (n = 3) were carried out to demonstrate the translational power of the USPIO-SWI method. By directly comparing the small vessel diameters of an in vivo rat using USPIO-SWI with the small vessel diameters of the corresponding histological slide using laser scanning confocal microscopy, 13.3-fold and 19.9-fold increases in SWI apparent diameter were obtained with 5.6 mg Fe/kg and 16.8 mg Fe/kg ferumoxytol, respectively. The USPIO-SWI method exhibited its excellent ability to detect small vessels down to about 10 μm diameter in rat brain. The in vivo human study unveiled hidden arterioles and venules and demonstrated its potential in clinical practice. Theoretical modeling simulations and in vitro phantom studies also confirmed a more than 10-fold increase in the USPIO-SWI apparent diameter compared with the actual small vessel diameter size. It is feasible to use SWI blooming effects induced by USPIO to detect small vessels (down to 10 μm in diameter for rat brain), well beyond the spatial resolution limit of conventional MRI methods. The USPIO-SWI method demonstrates higher potential in cerebrovascular disease investigations.

BACKGROUND:In neuromyelitis optica spectrum disorder (NMOSD), clinical disability in NMOSD patients is relapse-related and progressive phase is rare. This observation raises the question whether there is any radiographic disease activity. The aim of present study was to determine the longitudinal changes in cerebral lesion number, lesion size, lesion-to-venule relationship, and morphological patterns of lesions in NMOSD using multiparametric 7T MR imaging. We also aimed to assess brain volume changes in NMOSD. METHODS:A cohort of 22 patients with NMOSD underwent high-resolution 3D-susceptibility weighted imaging (SWI) and 2D-gradient-echo (GRE-T2*) weighted imaging on 7T MRI of brain at baseline and after ~2.8 years of follow-up. Morphologic imaging characteristics, and signal intensity patterns of lesions were recorded at both time points. Lesions were classified as "iron-laden" if they demonstrated hypointense signal on GRE-T2* images and/or SWI as well as hyperintense signal on quantitative susceptibility mapping (QSM). Lesions were considered "non-iron-laden" if they were hyperintense on GRE-T2*/SWI and isointense or hyperintense on QSM. Additionally, fractional brain parenchymal volume (fBPV) was computed at both time points. RESULTS:A total of 169 lesions were observed at baseline. At follow-up, 6 new lesions were found in 5 patients. In one patient, a single lesion could not be detected on the follow-up scan. No appreciable change in lesion size and vessel-lesion relationship was observed at follow up. All lesions demonstrated hyperintense signal intensity on GRE-T2* weighted images and isointense signal on QSM at both time points. Therefore, these lesions were considered as non-associated with iron pathology. Additionally, no significant change in brain volume was observed: fBPV 0.78 ± 0.06 at baseline vs. 0.77 ± 0.05 at follow up, p>0.05. CONCLUSION/CONCLUSIONS:Cerebral lesions in NMOSD patients remain 'inert' and do not show any substantial variations in morphological characteristics during a 2-3-year follow-up period.

BACKGROUND:Susceptibility weighted imaging (SWI) combines phase with magnitude information to better image sub-voxel veins. Recently, it has been extended to image very small sub-voxel arteries and veins by injecting intravenously the ultra-small superparamagnetic iron oxide, Ferumoxytol. OBJECTIVE:To determine practical experimental imaging parameters for sub-voxel cerebral vessels at 7 T. METHODS:(30 min) were used. Both SWI and quantitative susceptibility mapping (QSM) data were analyzed. Contrast-to-noise ratio (CNR) was measured and used to determine the optimal practical imaging parameters for detection of small cortical penetrating arteries. RESULTS:For a given spatial resolution with an aspect ratio (frequency: phase: slice) of 2:4:8 relative to the vessel size, we found the TE-dose index (TE x dose) must be at least 40 ms·mg/kg for both SWI and QSM to reveal the most vessels. The higher the TE-dose index, the better the image quality for both SWI and QSM up to 60 ms·mg/kg. CONCLUSIONS:There is an optimal TE-dose index for improved visualization of sub-voxel vessels. Choosing the smallest TE and the largest allowed dose made it possible to run the sequence efficiently. In practice, the aspect ratio of 2:4:8 and the TE-dose index ranging from 40 to 60 ms·mg/kg provided the optimal and most practical solution.

H MRI maps brain anatomy and pathology non-invasively through contrasts generated by exploiting inhomogeneities in tissue micro-environments. Inferring histopathological information from MRI findings, however, remains challenging due to the absence of direct links between MRI signals and specific tissue compartments. Here, we show that convolutional neural networks, developed using co-registered multi-contrast MRI and histological data of the mouse brain, can generate virtual histology from MRI results. Our networks provide maps that mirror histological stains for axons and myelin with enhanced specificity compared to existing MRI markers. Furthermore, by introducing random perturbations to the inputs, the relative contribution of each MRI contrast within the networks can be estimated and guide the optimization of MRI acquisition. We anticipate our method to be a starting point for translation of MRI results into easy-to-understand virtual histology for neurobiologists and provide resources for developing novel MRI contrasts

Objective: To establish a microbial limit test method for compound miconazole nitrate ointment.
Method(s): According to the Pharmacopoeia of the People's Republic of China and considering the physical and chemical characteristics of the ointment,the test product was treated by isopropyl tetradecanoate and bacteria free sodium chloride (pH 7. 0)-peptone buffer which contained 10% poly sorbitate 80, and the membrane filtration method was applied in microbial count test. At the same time,the control bacteria of Pseudomonasaeruginosa was detected by routine method, and the control bacteria of Staphylococcus aureus was tested by the culture medium dilution method combined with membrane filtration method.
Result(s):In the microbial counting part, each test bacterium was 0. 5-2. At the same time,the control bacteria of Pseudomonas aeruginosa could be detected by routine method and the control bacteria of Staphylococcus aureus could be tested by the culture medium dilution method combined with the membrane filtration method.
Conclusion(s): Appropriate pretreatment methods for test products might thoroughly remove the antibacterial properties of ointment and solve the problem of difficult filtering of samples. This method is reliable for microbial limit test.
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