Vascular Volume Fraction Research Articles

Industrial adaptability and outdoor durability of highland bamboo bundle laminated veneer lumber (HBLVL)

The industrial development of high-value bamboo fiber-based composites is a crucial direction for advancing the bamboo industry in Africa, and investigating the actual outdoor aging of materials could provide more accurate references for material design and applications. This study explored the adaptability of highland bamboo from Ethiopia in industrial moso bamboo bundle laminated veneer lumber (MBLVL) to develop unique the HBLVL products specific to Africa. The durability of samples was studied for one year in an outdoor environment. The results revealed that the vascular bundle volume fraction, flexural strength, and flexural modulus of highland bamboo (57.25 %, 193.89 MPa, and 18.47 GPa) were superior to those of moso bamboo (34.42 %, 140.81 MPa, and 10.25 GPa), and the HBLVL (168.98 MPa and 20.51 GPa) exhibited a higher flexural strength and flexural modulus than the MBLVL (117.60 MPa and 10.74 GPa). Although outdoor aging produced surface cracks, darker colors, and lignin degradation, the fundamental physical and mechanical properties of both the HBLVL and the MBLVL remained stable. This study's findings provide a theoretical basis for the efficient utilization of African bamboo resources and for the industrial production of the HBLVL, as well as experimental data for future outdoor aging research.

Age and anatomical region-related differences in vascularization of the porcine meniscus using microcomputed tomography imaging.

Meniscal lesions in vascularized regions are known to regenerate while lack of vascular supply leads to poor healing. Here, we developed and validated a novel methodology for three-dimensional structural analysis of meniscal vascular structures with high-resolution microcomputed tomography (µCT). We collected porcine medial menisci from 10 neonatal (not-developed meniscus, n-) and 10 adults (fully developed meniscus, a-). The menisci were cut into anatomical regions (anterior horn (n-AH anda-AH), central body (n-CB anda-CB), and posterior horn (n-PH anda-PH). Specimens were cut in half, fixed, and one specimen underwent critical point drying and µCT imaging, while other specimen underwent immunohistochemistry and vascularity biomarker CD31 staining for validation of µCT. Parameters describing vascular structures were calculated from µCT. The vascular network in neonatal spread throughout meniscus, while in adult was limited to a few vessels in outer region, mostly on femoral side. n-AH, n-CB, and n-PH had 20, 17, and 11 times greater vascular volume fraction than adult, respectively. Moreover, thickness of blood vessels, in three regions, was six times higher in adults than in neonatal. a-PH appeared to have higher vascular fraction, longer and thicker blood vessels than both a-AH and a-CB. Overall, neonatal regions had a higher number of blood vessels, more branching, and higher tortuosity compared to adult regions. For the first time, critical point drying-based µCT imaging allowed detailed three-dimensional visualization and quantitative analysis of vascularized meniscal structures. We showed more vascularity in neonatal menisci, while adult menisci had fewer and thicker vascularity especially limited to the femoral surface.

3D QUANTITATIVE CHARACTERIZATION OF THE HUMAN MENISCAL VASCULAR NETWORK USING X-RAY MICRO-COMPUTED TOMOGRAPHY

A comprehensive understanding of the self-repair abilities of menisci and their overall function in the knee joint requires three-dimensional information. However, previous investigations of the meniscal blood supply have been limited to two-dimensional imaging methods, which fail to accurately capture tissue complexity. In this study, micro-CT was used to analyse the 3D microvascular structure of the meniscus, providing a detailed visualization and precise quantification of the vascular network.A contrast agent (μAngiofil®) was injected directly into the femoral artery of cadaver legs to provide the proper contrast enhancement. First, the entire knee joint was analysed with micro-CT, then to increase the applicable resolution the lateral and medial menisci were excised and investigated with a maximum resolution of up to 4 μm. The resulting micro-CT datasets were analysed both qualitatively and quantitatively. Key parameters of the vascular network, such as vascular volume fraction, vessel radius, vessel length density, and tortuosity, were separately determined for the lateral and medial meniscus, and their four circumferential zones defined by Cooper.In accordance with previous literature, the quantitative micro-CT data confirm a decrease in vascular volume fraction along the meniscal zones. The highest concentration of blood vessels was measured in the meniscocapsular region 0, which is characterized by vascular segments with a significantly larger average radius. Furthermore, the highest vessel length density observed in zone 0 suggests a more rapid delivery of oxygen and nutrients compared to other regions. Vascular tortuosity was detected in all circumferential regions, indicating the occurrence of vascular remodelling in all tissue areas.In conclusion, micro-CT is a non-invasive imaging technique that allows for the visualization of the internal structure of an object in three dimensions. These advanced 3D vascular analyses have the potential to establish new surgical approaches that rely on the healing potential of specific areas of the meniscus.Acknowledgements: The authors acknowledge R. Hlushchuk, S. Halm, and O. Khoma from the University of Bern for their help with contrast agent perfusions.

PDZK1 is correlated with DCE-MRI perfusion parameters in high-grade glioma

ObjectiveThis study investigated the relationship between PDZK1 expression and Dynamic Contrast-Enhanced MRI (DCE-MRI) perfusion parameters in High-Grade Glioma (HGG). MethodsPreoperative DCE-MRI scanning was performed on 80 patients with HGG to obtain DCE perfusion transfer coefficient (Ktrans), vascular plasma volume fraction (vp), extracellular volume fraction (ve), and reverse transfer constant (kep). PDZK1 in HGG patients was detected, and its correlation with DCE-MRI perfusion parameters was assessed by the Pearson method. An analysis of Cox regression was performed to determine the risk factors affecting survival, while Kaplan-Meier and log-rank tests to evaluate PDZK1′s prognostic significance, and ROC curve analysis to assess its diagnostic value. ResultsPDZK1 was upregulated in HGG patients and predicted poor overall survival and progression-free survival. Moreover, PDZK1 expression distinguished grade III from grade IV HGG. PDZK1 expression was positively correlated with Ktrans 90, and ve_90, and negatively correlated with kep_max, and kep_90. ConclusionPDZK1 is upregulated in HGG, predicts poor survival, and differentiates tumor grading in HGG patients. PDZK1 expression is correlated with DCE-MRI perfusion parameters.

Effects of isopsoralen on tibial fracture and vascular healing in mice

To explore effects of isopsoralen (ISO) with different doses on fracture and vascular healing in mice. Sixty 2-month-old male C57BL/6 mices with body mass of (20±2) g were selected and divided into 4 groups by random number table method:model group (model), low dose group (isopsoralen-low dose, ISO-L), medium dose group (isopsoralen-medium dose, ISO-M) and high dose group (isopsoralen-high dose, ISO-H), with 15 animals in each group. The right tibial fracture model was established. After operation, ISO-L group, ISO-M group and ISO-H group were given ISO concentration of 10 mg·kg-1, 20 mg·kg-1 and 40 mg·kg-1, respectively. Model group was given same volume of normal saline once a day for 28 days. Weighed once a week. X-ray was performed on 7, 14, 21 and 28 days, respectively, and modified I.R. Garrett scoring method was used to evaluate callus growth. After 28 days, the main organs were stripped and weighed, and organ coefficients were calculated. Hematoxylin eosin staining (HE staining) was performed on the organs to observe whether there were pathological structural changes. Micro-computed tomography (Micro-CT) was used to scan fracture area and conduct three-dimensional reconstruction to obtain the effect map, and quantify bone volume fraction (bone volume/total volume, BV/TV). After decalcification, the tibia was embedded in paraffin wax and sectioned. The healing and shape of fracture end were observed by HE staining and ferruxin solid green staining. The right tibia was removed and decalcified after intravascular infusion of Microfil contrast agent. Micro-CT was used to scan the callus microvessels in the fracture area, and the vascular volume fraction and vessel diameter were quantified. After 28 days of administration, there was no significant difference in body mass and organ coefficient among all groups (P>0.05), and no significant pathological changes were found in HE staining of organs. The results of X-ray and improved I.R. Garrett score showed that ISO-M group was higher than that of Model group at 28 days (P<0.05). Scores of ISO-H group at 14, 21 and 28 days were higher than those of the other 3 groups (P<0.05). Micro-CT results showed intracavitary callus in ISO-M group was significantly reduced, which was lower than that in Model group (P<0.05), most of the callus in ISO-H group were subsided, and BV/TV in ISO-H group was lower than that in the other 3 groups (P<0.05). The results of HE staining and ferrubens solid green staining showed fracture area of ISO-H group was closed, continuous laminar bone had appeared, and the fracture healing process was higher than that of other groups. Angiographic results showed vascular volume fraction in ISO-H and ISO-M groups was higher than that in Model and ISO-L groups (P<0.05), and the vascular diameter in ISO-H and ISO-M groups was higher than that in Model and ISO-L groups (P<0.05). In the concentration range of 10-40 mg·kg-1, ISO has no obvious toxic and side effects, and could improve bone microstructure, promote formation of callus microvessels, and accelerate healing of fracture ends in a concentration-dependent manner.

The impact of vascular volume fraction and compressibility of the interstitial matrix on vascularised poroelastic tissues.

In this work we address the role of the microstructural properties of a vascularised poroelastic material, characterised by the coupling between a poroelastic matrix and a viscous fluid vessels network, on its overall response in terms of pressures, velocities and stress maps. We embrace the recently developed model (Penta and Merodio in Meccanica 52(14):3321-3343, 2017) as a theoretical starting point and present the results obtained by solving the full interplay between the microscale, represented by the intervessels' distance, and the macroscale, representing the size of the overall tissue. We encode the influence of the vessels' density and the poroelastic matrix compressibility in the poroelastic coefficients of the model, which are obtained by solving appropriate periodic cell problem at the microscale. The double-poroelastic model (Penta and Merodio 2017) is then solved at the macroscale in the context of vascular tumours, for different values of vessels' walls permeability. The results clearly indicate that improving the compressibility of the matrix and decreasing the vessels' density enhances the transvascular pressure difference and hence transport of fluid and drug within a tumour mass after a transient time. Our results suggest to combine vessel and interstitial normalization in tumours to allow for better drug delivery into the lesions.

A retrospective evaluation of Bayesian-penalized likelihood reconstruction for [15O]H2O myocardial perfusion imaging

BackgroundNew Block-Sequential-Regularized-Expectation-Maximization (BSREM) image reconstruction technique has been introduced for clinical use mainly for oncologic use. Accurate and quantitative image reconstruction is essential in myocardial perfusion imaging with positron emission tomography (PET) as it utilizes absolute quantitation of myocardial blood flow (MBF). The aim of the study was to evaluate BSREM reconstruction for quantitation in patients with suspected coronary artery disease (CAD). Methods and ResultsWe analyzed cardiac [15O]H2O PET studies of 177 patients evaluated for CAD. Differences between BSREM and Ordered-Subset-Expectation-Maximization with Time-Of-Flight (TOF) and Point-Spread-Function (PSF) modeling (OSEM-TOF-PSF) in terms of MBF, perfusable tissue fraction, and vascular volume fraction were measured. Classification of ischemia was assessed between the algorithms. OSEM-TOF-PSF and BSREM provided similar global stress MBF in patients with ischemia (1.84 ± 0.21 g⋅ml−1⋅min−1 vs 1.86 ± 0.21 g⋅ml−1⋅min−1) and no ischemia (3.26 ± 0.34 g⋅ml−1⋅min−1 vs 3.28 ± 0.34 g⋅ml−1⋅min−1). Global resting MBF was also similar (0.97 ± 0.12 g⋅ml−1⋅min−1 and 1.12 ± 0.06 g⋅ml−1⋅min−1). The largest mean relative difference in MBF values was 7%. Presence of myocardial ischemia was classified concordantly in 99% of patients using OSEM-TOF-PSF and BSREM reconstructions ConclusionOSEM-TOF-PSF and BSREM image reconstructions produce similar MBF values and diagnosis of myocardial ischemia in patients undergoing [15O]H2O PET due to suspected obstructive coronary artery disease

Morphological changes in the myocardium of rats with chronic alcohol intoxication after treatment with new GABAand glutamic acid derivatives

Aim. To study pathohistological changes in the myocardium of rats with chronic alcohol intoxication (CAI) after treatment with a new glutamic acid derivative glufimet (compound RSPU-238) and a new gamma-aminobutyric acid (GABA) derivative (compound RSPU-260).Materials and methods. Experiments were performed on female Wistar rats aged 10 months. The rats were divided into the following groups: group 1 – intact females; group 2 – a control group which included animals after CAI simulated by replacing drinking water with 10% ethanol solution for 24 weeks; groups 3 and 4 – experimental groups, in which females were intraperitoneally administered with glufimet at a dose of 28.7 mg / kg and RSPU260 at a dose of 25 mg / kg once a day for 14 days after cessation of alcohol solution consumption; group 5 – a group of animals receiving a reference listed drug mildronate at a dose of 50 mg / kg according to a regimen similar to that of the studied compounds. Changes in microstructural and morphometric parameters of the left ventricular myocardium were assessed using light microscopy.Results. In animals after CAI, the cardiomyocyte volume fraction decreased, while the interstitial and vascular volume fractions increased. Degeneration of cardiomyocytes, such as their wave-like deformation, loss of transverse striation, foci of plasmolysis, and fragmentation of muscle fibers were revealed. In rats treated with glufimet, the structural changes in cardiomyocytes were minimal. Lower vascular plethora was observed; blood vessels were characterized by single stasis and sludge. The cardiomyocyte volume fraction was 9.7% greater than in control animals, while the interstitial and vascular volume fractions were 66.0 and 70.0% smaller, respectively. The animals treated with the RSPU-260 compound had no significant degenerative changes in cardiomyocytes and small vessels similar to the experimental animals injected with glufimet. Mildronate had a less pronounced cardioprotective effect.Conclusion. Administration of new GABA and glutamic acid derivatives to animals with simulated chronic alcohol intoxication leads to improvement of the microstructure in cardiomyocytes compared with control rats. This indicates pronounced cardioprotective effects of the studied neuroactive amino acid derivatives.

Bridging the macro to micro resolution gap with angiographic optical coherence tomography and dynamic contrast enhanced MRI

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is emerging as a valuable tool for non-invasive volumetric monitoring of the tumor vascular status and its therapeutic response. However, clinical utility of DCE-MRI is challenged by uncertainty in its ability to quantify the tumor microvasculature (mu mathrm{m} scale) given its relatively poor spatial resolution (mm scale at best). To address this challenge, we directly compared DCE-MRI parameter maps with co-registered micron-scale-resolution speckle variance optical coherence tomography (svOCT) microvascular images in a window chamber tumor mouse model. Both semi and fully quantitative (Toft’s model) DCE-MRI metrics were tested for correlation with microvascular svOCT biomarkers. svOCT’s derived vascular volume fraction (VVF) and the mean distance to nearest vessel (overline{mathrm{DNV} }) metrics were correlated with DCE-MRI vascular biomarkers such as time to peak contrast enhancement (r=-0.81 and 0.83 respectively, P<0.0001 for both), the area under the gadolinium-time concentration curve (r=0.50 and -0.48 respectively, P<0.0001 for both) and {k}_{trans} (r=0.64 and -0.61 respectively, P<0.0001 for both). Several other correlated micro–macro vascular metric pairs were also noted. The microvascular insights afforded by svOCT may help improve the clinical utility of DCE-MRI for tissue functional status assessment and therapeutic response monitoring applications.

DCE-MRI of\xa0esophageal carcinoma using star-VIBE compared with\xa0conventional 3D-VIBE

To investigate the value of the star-VIBE sequence in dynamic contrast-enhanced magnetic resonance imaging of esophageal carcinoma under free breathing conditions. From February 2019 to June 2020, 60 patients with esophageal carcinoma were prospectively enrolled to undergo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with the K-space golden-angle radial stack-of-star acquisition scheme (star-VIBE) sequence (Group A) or conventional 3D volumetric-interpolated breath-hold examination (3D-VIBE) sequence (Group B), completely randomized grouping. The image quality of DCE-MRI was subjectively evaluated at five levels and objectively evaluated according to the image signal-to-noise ratio (SNR) and contrast-noise ratio (CNR). The DCE-MRI parameters of volume transfer constant (Ktrans), rate constant (Kep) and vascular extracellular volume fraction (Ve) were calculated using the standard Tofts double-compartment model in the post-perfusion treatment software TISSUE 4D (Siemens). Each group included 30 randomly selected cases. There was a significant difference in subjective classification between the groups (35.90 vs 25.10, p = 0.009). The study showed that both the SNR and CNR of group A were significantly higher than those of group B (p = 0.004 and < 0.001, respectively). There was no significant difference in Ktrans, Kep or Ve between the groups (all p > 0.05). The star-VIBE sequence can be applied in DCE-MRI examination of esophageal carcinoma, which can provide higher image quality than the conventional 3D-VIBE sequence in the free breathing state.

Multiparametric Magnetic Resonance Imaging for Immediate Target Hit Assessment of CD13-Targeted Tissue Factor tTF-NGR in Advanced Malignant Disease.

Simple SummarySince the knowledge of tumor biology has advanced, a variety of targeted therapies has been developed. These do not immediately affect the tumor size, so optimized oncological imaging is needed. In this phase I study of patients with advanced malignant disease, a multiparametric imaging approach was used to assess changes in tumor perfusion after vessel-occluding therapy with the CD13 targeted truncated tissue factor with a C-terminal NGR-peptide. It comprises different sequences and the use of two different contrast media, ferucarbotran and gadobutrol. This multiparametric MRI protocol enables assessing the therapy effectiveness as early as five hours after therapy initiation.Early assessment of target hit in anti-cancer therapies is a major task in oncologic imaging. In this study, immediate target hit and effectiveness of CD13-targeted tissue factor tTF-NGR in patients with advanced malignant disease enrolled in a phase I trial was assessed using a multiparametric MRI protocol. Seventeen patients with advanced solid malignancies were enrolled in the trial and received tTF-NGR for at least one cycle of five daily infusions. Tumor target lesions were imaged with multiparametric MRI before therapy initiation, five hours after the first infusion and after five days. The imaging protocol comprised ADC, calculated from DWI, and DCE imaging and vascular volume fraction (VVF) assessment. DCE and VVF values decreased within 5 h after therapy initiation, indicating early target hit with a subsequent decrease in tumor perfusion due to selective tumor vessel occlusion and thrombosis induced by tTF-NGR. Simultaneously, ADC values increased at five hours after tTF-NGR administration. In four patients, treatment had to be stopped due to an increase in troponin T hs, with subsequent anticoagulation. In these patients, a reversed effect, with DCE and VVF values increasing and ADC values decreasing, was observed after anticoagulation. Changes in imaging parameters were independent of the mean vessel density determined by immunohistochemistry. By using a multiparametric imaging approach, changes in tumor perfusion after initiation of a tumor vessel occluding therapy can be evaluated as early as five hours after therapy initiation, enabling early assessment of target hit.

Hierarchical imaging and computational analysis of three-dimensional vascular network architecture in the entire postnatal and adult mouse brain.

The formation of new blood vessels and the establishment of vascular networks are crucial during brain development, in the adult healthy brain, as well as in various diseases of the central nervous system. Here, we describe a step-by-step protocol for our recently developed method that enables hierarchical imaging and computational analysis of vascular networks in postnatal and adult mouse brains. The different stages of the procedure include resin-based vascular corrosion casting, scanning electron microscopy, synchrotron radiation and desktop microcomputed tomography imaging, and computational network analysis. Combining these methods enables detailed visualization and quantification of the 3D brain vasculature. Network features such as vascular volume fraction, branch point density, vessel diameter, length, tortuosity and directionality as well as extravascular distance can be obtained at any developmental stage from the early postnatal to the adult brain. This approach can be used to provide a detailed morphological atlas of the entire mouse brain vasculature at both the postnatal and the adult stage of development. Our protocol allows the characterization of brain vascular networks separately for capillaries and noncapillaries. The entire protocol, from mouse perfusion to vessel network analysis, takes ~10 d.

Crossed cerebellar diaschisis after acute ischemic stroke detected by intravoxel incoherent motion magnetic resonance imaging

To study the value of 3.0T magnetic resonance imaging with intravoxel incoherent motion (IVIM) in the diagnosis of the crossed cerebellar diaschisis (CCD) after the unilateral supratentorial acute ischemic stroke. Seventy-four patients with acute ischemic stroke who underwent intravoxel incoherent motion (IVIM), arterial spin labeling (ASL), and conventional magnetic resonance imaging (MRI) scanning were enrolled. Intravoxel incoherent motion-derived perfusion-related parameters including fast diffusion coefficient (D*), slow diffusion coefficient (D), vascular volume fraction (f), and arterial spin-labeling-derived cerebral blood flow (CBF) of bilateral cerebellum were measured. In the CCD-positive group, D*, D, and CBF values of the contralateral cerebellum decreased compared with those of the ipsilesional cerebellum (P < 0.05), whereas f significantly increased (P < 0.05). A positive correlation was detected between the slow diffusion coefficient-based asymmetry index (AI-D) and the cerebral blood flow-based asymmetry index (AI-CBF) (r = 0.515, P < 0.01), whereas the vascular volume fraction-based asymmetry index (AI-f) had a negative correlation with the cerebral blood flow-based asymmetry index (AI-CBF) (r = - 0.485, P < 0.01). Furthermore, the area under the receiver operating characteristic (ROC) curve value of AI-D and AI-f was 0.81 and 0.76, respectively. The IVIM is feasible for the detection of CCD. This technique might provide opportunities to further investigate the pathophysiology of CCD.

Spectral diffusion analysis of kidney intravoxel incoherent motion MRI in healthy volunteers and patients with renal pathologies.

To assess the feasibility of measuring tubular and vascular signal fractions in the human kidney using nonnegative least-square (NNLS) analysis of intravoxel incoherent motion data collected in healthy volunteers and patients with renal pathologies. MR imaging was performed at 3 Tesla in 12 healthy subjects and 3 patients with various kidney pathologies (fibrotic kidney disease, failed renal graft, and renal masses). Relative signal fractions f and mean diffusivities of the diffusion components in the cortex, medulla, and renal lesions were obtained using the regularized NNLS fitting of the intravoxel incoherent motion data. Test-retest repeatability of the NNLS approach was tested in 5 volunteers scanned twice. In the healthy kidneys, the NNLS method yielded diffusion spectra with 3 distinguishable components that may be linked to the slow tissue water diffusion, intermediate tubular and vascular flow, and fast blood flow in larger vessels with the relative signal fractions, fslow , finterm and ffast , respectively. In the pathological kidneys, the diffusion spectra varied substantially from those acquired in the healthy kidneys. Overall, the renal cyst showed substantially higher finterm and lower fslow , whereas the fibrotic kidney, failed renal graft, and renal cell carcinoma demonstrated the opposite trend. NNLS-based intravoxel incoherent motion could potentially become a valuable tool in assessing changes in tubular and vascular volume fractions under pathophysiological conditions.

Effect of Beta-Blocker Cardioselectivity on Vascular Refilling in Hemodialysis Patients

Background: β-Blockers are the most frequently prescribed cardioprotective drugs in hemodialysis (HD) patients, despite their weak evidence. We sought to evaluate the effects of β-blockers on vascular refilling during HD treatments and examine whether carvedilol, for being noncardioselective and poorly dialyzable, associates more impact than others. Methods: The study was performed in a cohort of maintenance HD patients from a tertiary center. All patients had previous β-blocker prescription. We conducted a prospective crossover study and measured vascular refilling volume (V_ref) and vascular refilling fraction (F_ref) in 2 circumstances: under β-blocker treatment (βb profile) and without β-blocker effect (non-βb profile). Results: Twenty patients were included, 10 of whom were treated with carvedilol. Predialysis values were comparable between the 2 profiles. Although the βb profile showed lower V_ref and higher ABV drop, these differences did not reach statistical significance. Data showed an increase in F_ref in the non-βb profile (70.01 ± 6.80% vs. 63.14 ± 11.65%; p = 0.015). The βb profile associated a significantly higher risk of intradialytic hypotension (IDH) (risk ratio 2.40; 95% CI: 1.04–5.55). When analyzing separately the carvedilol group, patients dialyzed under drug effect experienced a significant impairment in V_ref, F_ref, and refilling rate. Conclusions: Administering β-blockers before HD associated a higher risk of IDH and a decrease in F_ref. Patients dialyzed under carvedilol effect showed an impaired refilling, probably related to its noncardioselectivity and lower dializability.

Cerebral microvascular and microstructural integrity is regionally altered in patients with systemic lupus erythematosus

BackgroundTo measure regional brain microvascular and microstructural changes in childhood-onset SLE (cSLE) using diffusion-weighted imaging (DWI) at multiple b values and investigate relationships of those measures with neurocognitive function and disease activity.MethodsIn this cross-sectional, case-control study, vascular volume fraction, effective diffusion, parenchymal diffusion, and blood flow parameters were regionally compared in cSLE patients and matched healthy controls. These markers of microvascular and microstructural integrity were derived by diffusion-weighted brain MRI and intravoxel incoherent motion (IVIM) modeling. Formal neurocognitive testing was completed focused on the domains of attention, visuoconstructional ability, working memory, and psychomotor speed. Test scores and measures of disease severity were regressed against regional microvascular integrity parameters among cSLE patients.ResultsFormal cognitive testing confirmed normal cognitive ability among all cSLE patients included in the analysis (n = 11). Nevertheless, reduction in blood volume fraction coincided with increased effective diffusion and flow parameters in cSLE patients vs. controls in posterior brain regions including the cuneus and precuneus. Regional microvascular measures correlated (|r| = 0.54–0.66) with neuropsychiatric scores and disease activity among cSLE patients.ConclusionsThere is imaging evidence, using IVIM, of degraded microvascular integrity in cSLE patients with normal cognitive ability. The observed regional changes correspond with posterior vascular border zones. These outcomes appear consistent with regional gray matter volume loss previously observed in cSLE patients with overt neurocognitive deficits, supporting the notion that adverse vascular changes precede loss of cognitive ability in cSLE. Longitudinal studies are needed to confirm the findings of this initial study.

High-resolution mapping of brain vasculature and its impairment in the hippocampus of Alzheimer's disease mice

Accumulating evidence indicates the critical importance of cerebrovascular dysfunction in the pathogenesis of Alzheimer's disease (AD). However, systematic comparative studies on the precise brain vasculature of wild-type and AD model mice are still rare. Using an image-optimization method for analysing Micro-Optical Sectioning Tomography (MOST) data, we generated cross-scale whole-brain 3D atlases that cover the entire vascular system from large vessels down to smallest capillaries at submicron resolution, for both wild-type mice and a transgenic (APP/PS1) mouse model of AD. In addition to distinct vascular patterns in different brain regions, we found that the main vessels of the molecular layer of the hippocampal dentate gyrus (DG-ml) undergo abrupt changes in both diameter and branch angle, spreading a unique comb-like pattern of capillaries. By using a quantitative analysis workflow, we identified in the hippocampus of AD mice an overall reduction of the mean vascular diameter, volume fraction and branch angle, with most significant impairment in the DG-ml. In addition, virtual endoscopy revealed irregular morphological features in the vessel lumen of the AD mice, potentially contributing to the impairment of blood flow. Our results demonstrate the capability of high-resolution cross-scale evaluation of brain vasculature and underscore the importance of studying hippocampal microcirculation for understanding AD pathogenesis.

Detection of Crossed Cerebellar Diaschisis by Intravoxel Incoherent Motion MR Imaging in Subacute Ischemic Stroke

Intravoxel incoherent motion has received extensive attention in brain studies for its potential as a non-invasive magnetic resonance perfusion method. However, studies on intravoxel incoherent motion imaging and crossed cerebellar diaschisis detection are relatively scarce. The aim of our study was to evaluate the feasibility of using intravoxel incoherent motion imaging in crossed cerebellar diaschisis diagnosis in subacute ischemic stroke patients by comparing results from intravoxel incoherent motion imaging, single-photon emission computed tomography, and arterial spin-labeling perfusion methods. In total, 39 patients with subacute ischemic stroke who underwent intravoxel incoherent motion, arterial spin-labeling, and single-photon emission computed tomography scanning were enrolled. Intravoxel incoherent motion-derived perfusion-related parameters including fast diffusion coefficient, vascular volume fraction, arterial spin-labeling-derived cerebral blood flow as well as single-photon emission computed tomography-derived cerebral blood flow of bilateral cerebellum were measured. A crossed cerebellar diaschisis-positive result was considered present with an asymmetry index ≥10% of single-photon emission computed tomography. In the crossed cerebellar diaschisis-positive group, fast diffusion coefficient, arterial spin-labeling-derived cerebral blood flow, and computed tomography-derived cerebral blood flow of the contralateral cerebellum decreased compared with those of the ipsilesional cerebellum; whereas vascular volume fraction significantly increased. The National Institutes of Health Stroke Scale score and infarct volume in the crossed cerebellar diaschisis-positive group were significantly higher than those in the crossed cerebellar diaschisis-negative group. A positive correlation was detected between the fast diffusion coefficient-based asymmetry index and the single-photon emission computed tomography-based asymmetry index, fast diffusion coefficient-based asymmetry, and arterial spin-labeling based asymmetry index; whereas the vascular volume fraction-based asymmetry index value had a negative correlation with the single-photon emission computed tomography-based asymmetry index and arterial spin-labeling based asymmetry index. Furthermore, the area under the receiver operating characteristic curve value of the arterial spin-labeling-based asymmetry index was 0.923. The fast diffusion coefficient derived from the intravoxel incoherent motion could be valuable for the assessment of crossed cerebellar diaschisis in supratentorial stroke patients.

Multi-parametric FDG PET/MRI as an early predictor of response to neoadjuvant chemotherapy in patients with epithelial ovarian cancer.

5569 Background: For patients with ovarian cancer undergoing neoadjuvant chemotherapy, the effectiveness of treatment is not evaluable by conventional methods until all or much of the treatment has been given. The purpose of this study is to investigate the performance of FDG PET, dynamic contrast-enhanced (DCE) and intra-voxel incoherent motion (IVIM) MR as early predictors of treatment response. Methods: Subjects with a new diagnosis of epithelial ovarian cancer underwent 3 cycles of standardized chemotherapy followed by cytoreduction. FDG PET/MR including DCE and IVIM was performed at baseline (T0), after cycle 1 (T1) and after cycle 3 (T2) of chemotherapy. Final responses were categorized at T2 by RECIST 1.1. Image volumes at T1 were analyzed as predictors of final response. Parametric images of molecular diffusion restriction (D), tissue perfusion (D*), vascular volume fraction (F), blood- &gt; interstitium constant of transfer (Ktrans), interstitum- &gt; plasma constant of transfer (Kep), extravascular/extracellular volume % (Ve) and plasma volume % (Ve) were investigated along with routine measures of SUV and ADC. Results: Nine subjects were enrolled, 8 were responders by RECIST at T2 and one had stable disease. At T0 the mean, min, and max SUVmax of dominant tumor deposits was 11.5, 6.3, 19.0, respectively. Mean, min, and max values were 1.0, 0.75 and 1.63 for ADCmean and 0.62, 0.30, 0.96 for ADCmin. At T1, ADCmean increased in 8 subjects by +0.22% (s.d. +/- 13%) and decreased by -3% in one subject. ADCmin increased in 8 subjects by +21% (s.d. +/-11%) and decreased by -23% in one subject. D increased for 8 subjects (average +29% s.d. +/- 13%) and decreased by -10% in one. D*, F, Kep, Ktrans, Ve and Vp had no recognizable pattern. At T2, SUVmax, SUVmin, and ADCmean maintained their change direction across all subjects with measurable lesions. The only subject with a complete response at T2 had the highest ADCmin and ADCmean change at +45% after one cycle of chemotherapy (T1). The subject with stable disease at T2 had no significant difference in changes amongst all metrics. Conclusions: FDG PET/MR SUVmax and ADCmean values obtained after one cycle of neoadjuvant chemotherapy were consistently associated with partial anatomical treatment responses after three cycles. Molecular diffusion restriction also was reliably associated with treatment response. Future studies evaluating FDG PET/MR in platinum-resistant patients may allow for early discontinuation of ineffective and toxic treatment.

Anisotropic elastic properties of human femoral cortical bone and relationships with composition and microstructure in elderly

The strong dependence between cortical bone elasticity at the millimetre-scale (mesoscale) and cortical porosity has been evidenced by previous studies. However, bone is an anisotropic composite material made by mineral, proteins and water assembled in a hierarchical structure. Whether the variations of structural and compositional properties of bone affect the different elastic coefficients at the mesoscale is not clear. Aiming to understand the relationships between bone elastic properties and compositions and microstructure, we applied state-of-the-art experimental modalities to assess these aspects of bone characteristics. All elastic coefficients (stiffness tensor of the transverse isotropic bone material), structure of the vascular pore network, collagen and mineral properties were measured in 52 specimens from the femoral diaphysis of 26 elderly donors. Statistical analyses and micromechanical modeling showed that vascular pore volume fraction and the degree of mineralization of bone are the most important determinants of cortical bone anisotropic mesoscopic elasticity. Though significant correlations were observed between collagen properties and elasticity, their effects in bone mesoscopic elasticity were minor in our data. This work also provides a unique set of data exhibiting a range of variations of compositional and microstructural cortical bone properties in the elderly and gives strong experimental evidence and basis for further development of biomechanical models for human cortical bone. Statement of SignificanceThis study reports the relationships between microstructure, composition and the mesoscale anisotropic elastic properties of human femoral cortical bone in elderly. For the first time, we provide data covering the complete anisotropic elastic tensor, the microstructure of cortical vascular porosity, mineral and collagen characteristics obtained from the same or adjacent samples in each donor. The results revealed that cortical vascular porosity and degree of mineralization of bone are the most important determinants of bone anisotropic stiffness at the mesoscale. The presented data gives strong experimental evidence and basis for further development of biomechanical models for human cortical bone.