Identifying the neural correlates of anticipatory postural control: A novel fMRI paradigm.

Altered postural control in the trunk/hip musculature is a characteristic of multiple neurological and musculoskeletal conditions. Previously it was not possible to determine if altered cortical and subcortical sensorimotor brain activation underlies impairments in postural control. This study used a novel fMRI-compatible paradigm to identify the brain activation associated with postural control in the trunk and hip musculature. BOLD fMRI imaging was conducted as participants performed two versions of a lower limb task involving lifting the left leg to touch the foot to a target. For the supported leg raise (SLR) the leg is raised from the knee while the thigh remains supported. For the unsupported leg raise (ULR) the leg is raised from the hip, requiring postural muscle activation in the abdominal/hip extensor musculature. Significant brain activation during the SLR task occurred predominantly in the right primary and secondary sensorimotor cortical regions. Brain activation during the ULR task occurred bilaterally in the primary and secondary sensorimotor cortical regions, as well as cerebellum and putamen. In comparison with the SLR, the ULR was associated with significantly greater activation in the right premotor/SMA, left primary motor and cingulate cortices, primary somatosensory cortex, supramarginal gyrus/parietal operculum, superior parietal lobule, cerebellar vermis, and cerebellar hemispheres. Cortical and subcortical regions activated during the ULR, but not during the SLR, were consistent with the planning, and execution of a task involving multisegmental, bilateral postural control. Future studies using this paradigm will determine mechanisms underlying impaired postural control in patients with neurological and musculoskeletal dysfunction.

Improving the detection specificity of endogenous MRI for reactive oxygen species (ROS).

BACKGROUND: The detection of tissue reactive oxygen species (ROS) using endogenous MRI methods has great potential applications in research and the clinic. We recently demonstrated that ROS produce a significant T1 -shortening effect. However, T1 or T1 -weighted contrast is not specific, as there are many other factors that alter tissue T1 . PURPOSE: To investigate whether the presence of ROS alters tissue environmental conditions such as the proton exchange rate (K ex ) to improve the detection specificity of endogenous ROS MRI. STUDY TYPE: Prospective. SUBJECTS/PHANTOM: The ROS-producing phantoms consisted of fresh egg white treated with H2 O2 and healthy mice injected with pro-oxidative rotenone. FIELD STRENGTH/SEQUENCE: T1 mapping was performed based on fast spin-echo sequence and K ex was evaluated using chemical exchange saturation transfer (CEST) MRI with varied saturation power (QUESP) on a 9.4 T animal scanner. ASSESSMENT: Phantom experiments were conducted to evaluate the overall K ex of CEST-expressing metabolites in fresh egg white treated with H2 O2 of various concentrations (0, 0.025, 0.05, 0.1, and 0.25 v/v%). The egg white phantom continuously produced ROS for more than 3 hours. Various experiments were performed to rule out potential contributing factors to the observed K ex changes. In addition, in vivo MRI study was conducted with a well-established rotenone-exposed mouse model. STATISTICAL TESTS: Student's t-test. RESULTS: Egg white phantoms treated with H2 O2 of various concentrations showed a 26-85% increase in K ex compared with controls. In addition, the K ex of egg white is negligibly affected by other potential confounding factors, including paramagnetic contrast agents (<11%), oxygen (2.3%), and iron oxidation (<10%). Changes in temperature (<1°C) and pH (ΔpH <0.1) in H2 O2 -treated egg white were also negligible. Results from the in vivo rotenone study were consistent with the phantom studies by showing reduced T1 relaxation time (6%) and increased K ex (9%) in rotenone-treated mice. DATA CONCLUSION: We demonstrate that the specificity of endogenous ROS MRI can be improved with the aid of proton exchange rate mapping. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:583-591.

Imaging short-lived reactive oxygen species (ROS) with endogenous contrast MRI.

PURPOSE: To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI). MATERIALS AND METHODS: ROS-producing phantoms and animal models were imaged at 9.4T MRI to obtain T1 and T2 maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H2 O2 ) were used to evaluate the effect of produced ROS in T1 and T2 for up to 4 hours. pH and temperature changes due to H2 O2 treatment in egg white were also monitored. The influences from H2 O2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T1 in H2 O2 -treated egg white samples were used to estimate ROS concentration over time and hence the detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of in vivo ROS MRI with T1 mapping acquired using an inversion recovery sequence was demonstrated with a well-established rotenone-treated mouse model (n = 6). RESULTS: pH and temperature changes in treated egg white samples were insignificant (<0.1 unit and <1°C, respectively). T1 relaxation time in the H2 O2 -treated egg white was reduced significantly (P < 0.05), while there was only small reduction in T2 (<10%). In the H2 O2 -treated BSA solution that produce no ROS, there was a small change in T1 due to H2 O2 itself (±1%), although a significant T2 -shortening effect was observed (>10%, P < 0.05). Also, there was a small reduction in T1 (13 ± 1%) and T2 (1 ± 2%) from molecular oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T1 relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 × 107 vs. 0.9 s-1 ·mM-1 ). Finally, significantly reduced T1 was observed in rotenone-treated mouse brain (5.1 ± 2.5%, P < 0.05). CONCLUSION: We demonstrated in the study that endogenous ROS MRI based on the paramagnetic effect has sensitivity for in vitro and in vivo applications. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2018;47:222-229.

Mapping brown adipose tissue based on fat water fraction provided by Z-spectral imaging.

BACKGROUND: Brown adipose tissue (BAT) has a great relevance in metabolic diseases and has been shown to be reduced in obesity and insulin resistance patients. Currently, Dixon MRI is used to calculate fat-water fraction (FWF) and differentiate BAT from white adipose tissue (WAT). However, it may fail in areas of phase wrapping and introduce fat-water swapping artifacts. PURPOSE: To investigate the capacity of the Z-spectrum imaging (ZSI) for the identification of BAT in vivo. STUDY TYPE: Retrospective study. SPECIMENS: WAT, BAT, and lean tissue from healthy mice. ANIMALS: Four C57BL/6 healthy mice. POPULATION: Five healthy volunteers. FIELD STRENGTH: 9.4T, 3T for volunteers. SEQUENCE: Z-Spectra data were fitted to a model with three Lorentzian peaks reflecting the direct saturation of tissue water (W) and methylene fat (F), and the magnetization transfer from the semi-solid tissues. The peak amplitudes of water and fat were used to map the FWF. The novel FWF metric was calibrated with an oil and water mixture phantom and validated in specimens, mice and human subjects. ASSESSMEMT: FWF distribution was compared with published works and values compared with Dixon's MRI results. STATISTICAL TESTS: Comparisons were performed by t-tests. RESULTS: ZSI clearly differentiated WAT, BAT, and lean tissues by having FWF = 1, 0.5, and 0, respectively. Calibration with oil mixture phantoms revealed a linear relationship between FWF and the actual fat fraction (R2 = 0.98). In vivo experiments in mice confirmed in vitro results by showing FWF = 0.6 in BAT. FWF maps of human subjects showed the same FWF distribution as Dixon's MRI (P > 0.05). ZSI is independent from B0 field inhomogeneity and fat-water swapping because both lipid and water frequency offsets are determined simultaneously during Z-spectral fitting. DATA CONCLUSION: ZSI can derive artifact-free FWF maps, which can be used to identify BAT distribution in vivo noninvasively. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1527-1533.

Influence of Free Radicals on the Intrinsic MRI Relaxation Properties.

Free radicals are critical contributors in various conditions including normal aging, Alzheimer's disease, cancer, and diabetes. Currently there is no non-invasive approach to image tissue free radicals based on endogenous contrast due to their extremely short lifetimes and low in vivo concentrations. In this study we aim at characterizing the influence of free radicals on the MRI relaxation properties. Phantoms containing free radicals were created by treating egg white with various H 2 O 2 concentrations and scanned on a 9.4 T MRI scanner at room temperature. T1 and T2 relaxation maps were generated from data acquired with an inversion recovery sequence with varied inversion times and a multi-echo spin echo sequence with varied echo times (TEs), respectively. Results demonstrated that free radicals express a strong shortening effect on T1, which was proportional to the H 2 O 2 concentration, and a relatively small reduction in T2 (<10%). Furthermore, the sensitivity of this approach in the detection of free radicals was estimated to be in the pM range that is within the physiological range of in vivo free radical expression. In conclusion, the free radicals show a strong paramagnetic effect that may be utilized as an endogenous MRI contrast for its non-invasive in vivo imaging.

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.

Negative emotions enhance memory-guided attention in a visual search task by increasing frontoparietal, insular, and parahippocampal cortical activity.

Previous literature demonstrated that long-term memory representations guide spatial attention during visual search in real-world pictures. However, it is currently unknown whether memory-guided visual search is affected by the emotional content of the picture. During functional magnetic resonance imaging (fMRI), participants were asked to encode the position of high-contrast targets embedded in emotional (negative or positive) or neutral pictures. At retrieval, they performed a visual search for targets presented at the same location as during encoding, but at a much lower contrast. Behaviorally, participants detected more accurately targets presented in negative pictures compared to those in positive or neutral pictures. They were also faster in detecting targets presented at encoding in emotional (negative or positive) pictures than in neutral pictures, or targets not presented during encoding (i.e., memory-guided attention effect). At the neural level, we found increased activation in a large circuit of regions involving the dorsal and ventral frontoparietal cortex, insular and parahippocampal cortex, selectively during the detection of targets presented in negative pictures during encoding. We propose that these regions might form an integrated neural circuit recruited to select and process previously encoded target locations (i.e., memory-guided attention sustained by the frontoparietal cortex) embedded in emotional contexts (i.e., emotional contexts recollection supported by the parahippocampal cortex and emotional monitoring supported by the insular cortex). Ultimately, these findings reveal that negative emotions can enhance memory-guided visual search performance by increasing neural activity in a large-scale brain circuit, contributing to disentangle the complex relationship between emotion, attention, and memory.

Inter- and intra-rater reliability of blood and cerebrospinal fluid flow quantification by phase-contrast MRI.

PURPOSE: To evaluate the intra- and inter-rater reliability of the quantification of blood and CSF flow rates by phase contrast MRI. MATERIALS AND METHODS: Blood and CSF flows in the upper cervical region were imaged with velocity-encoded cine-phase contrast using 3T scanners from different manufacturers at two centers. Data of 6 subjects scanned in center A and of 5 subjects in center B were analyzed by six readers at two levels of training. Each data set was analyzed three times in a randomized order for a total of 33 data sets. Intra-class correlation coefficients (ICC) were calculated for the primary measurements of areas and flow rates through the main cervical arteries, veins and the CSF space, and for secondary parameters derived from the individual flow rates. RESULTS: ICC ranged from 0.80 to 0.96 for the lumen area and from 0.97 to 0.99 for the volumetric flow rate. The ICC for the derived secondary measures ranged from 0.85 to 0.99. Differences due to operator level of training were not statistically significant. CONCLUSION: High intra- and inter-rater reliability of volumetric flow rate measurements is currently achievable across manufacturers and users' skill levels with a pulsatility based automated lumen segmentation.

Electroacupuncture for the management of symptom clusters in cancer patients and survivors (EAST).

BACKGROUND: Neuropsychiatric symptoms, comprising cognitive impairment, fatigue, insomnia, depression, and anxiety, are prevalent and may co-occur during and after chemotherapy treatment for cancer. Electroacupuncture (EA), which involves mild electrical stimulation with acupuncture, holds great potential in addressing the management of individual symptoms. However, there is a lack of studies evaluating if EA can manage concurrent neuropsychiatric symptoms in cancer (i.e., symptom cluster). Hence, we designed a trial to evaluate the efficacy, safety, and feasibility of administering EA as an intervention to mitigate neuropsychiatric symptom clusters amongst cancer patients and survivors. METHODS: The EAST study is a randomized, sham-controlled, patient- and assessor-blinded clinical trial. Sixty-four cancer patients and survivors with complaints of one or more neuropsychiatric symptom(s) in the seven days prior to enrollment are recruited from the University of California Irvine (UCI) and Children's Hospital of Orange County (CHOC). Individuals with needle phobia, metastases, bleeding disorders, electronic implants, epilepsy, exposure to acupuncture in the three months prior to enrollment, and who are breastfeeding, pregnant, or planning to get pregnant during the duration of the study will be excluded. Screening for metal fragments and claustrophobia are performed prior to the optional neuroimaging procedures. Recruited patients will be randomized (1:1) in random blocks of four or six to receive either ten weekly verum EA (treatment arm, vEA) or weekly sham EA (control arm, sEA) treatment visits with a follow-up appointment four to twelve weeks after their last treatment visit. The treatment arm will receive EA at 13 acupuncture points (acupoints) chosen for their therapeutic effects, while the control arm receives minimal EA at 7 non-disease-related acupoints. Questionnaires and cognitive assessments are administered, and blood drawn to assess changes in symptom clusters and biomarkers, respectively. CONCLUSION: The EAST study can provide insight into the efficacy of EA, an integrative medicine modality, in the management of cancer symptom clusters in routine clinical practice. TRIAL REGISTRATION: This trial is registered with clinicaltrials.gov NCT05283577.

Evidence for altered spinal canal compliance and cerebral venous drainage in untreated idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH), or pseudotumor cerebri, is a debilitating neurological disorder characterized by elevated CSF pressure of unknown cause. IIH manifests as severe headaches, and visual impairments. Most typically, IIH prevails in overweight females of childbearing age and its incidence is rising in parallel with the obesity epidemic. The most accepted theory for the cause of IIH is reduced absorption of CSF due to elevated intracranial venous pressure. A comprehensive MRI study, which includes structural and physiological imaging, was applied to characterize morphological and physiological differences between a homogeneous cohort of female IIH patients and an age- and BMI-similar control group to further elucidate the underlying pathophysiology. A novel analysis of MRI measurements of blood and CSF flow to and from the cranial and spinal canal compartments employing lumped parameters modeling of the cranio-spinal biomechanics provided, for the first time, evidence for the involvement of the spinal canal compartment. The CSF space in the spinal canal is less confined by bony structures compared with the cranial CSF, thereby providing most of the craniospinal compliance. This study demonstrates that the contribution of spinal canal compliance in IIH is significantly reduced.

Determination of cranio-spinal canal compliance distribution by MRI: Methodology and early application in idiopathic intracranial hypertension.

PURPOSE: To develop a method for derivation of the cranial-spinal compliance distribution, assess its reliability, and apply to obese female patients with a diagnosis of idiopathic intracranial hypertension (IIH). MATERIALS AND METHODS: Phase contrast-based measurements of blood and cerebrospinal fluid (CSF) flows to, from, and between the cranial and spinal canal compartments were used with lumped-parameter modeling to estimate systolic volume and pressure changes from which cranial and spinal compliance indices are obtained. The proposed MRI indices are analogous to pressure volume indices (PVI) currently being measured invasively with infusion-based techniques. The consistency of the proposed method was assessed using MRI data from seven aged healthy subjects. Measurement reproducibility was assessed using five repeated MR scans from one subject. The method was then applied to compare spinal canal compliance contribution in seven IIH patients and six matched healthy controls. RESULTS: In the healthy subjects, as expected, spinal canal contribution was consistently larger than the cranial contribution (average value of 69%). Measurement variability was 8%. In IIH, the spinal canal contribution is significantly smaller than normal controls (60 versus 78%, P < 0.03). CONCLUSION: An MRI-based method for derivation of compliance indices analogous to PVI has been implemented and applied to healthy subjects. The application of the method to obese IIH patients suggests a spinal canal involvement in the pathophysiology of IIH.

Evaluation of B0-correction of relative CBF maps using tagging distance dependent Z-spectrum (TADDZ).

Arterial spin labeling (ASL) MRI, based on endogenous contrast from blood water, is used in research and diagnosis of cerebral vascular conditions. However, artifacts due to imperfect imaging conditions such as B0-inhomogeneity (ΔB0) could lead to variations in the quantification of relative cerebral blood flow (CBF). In this study, we evaluate a new approach using tagging distance dependent Z-spectrum (TADDZ) data, similar to the ΔB0 corrections in the chemical exchange saturation transfer (CEST) experiments, to remove the imaging plane B0 inhomogeneity induced CBF artifacts in ASL MRI. Our results indicate that imaging-plane B0-inhomogeneity can lead to variations and errors in the relative CBF maps especially under small tagging distances. Along with an acquired B0 map, TADDZ data helps to eliminate B0-inhomogeneity induced artifacts in the resulting relative CBF maps. We demonstrated the effective use of TADDZ data to reduce variation while subjected to systematic changes in ΔB0. In addition, TADDZ corrected ASL MRI, with improved consistency, was shown to outperform conventional ASL MRI by differentiating the subtle CBF difference in Alzheimer's disease (AD) mice brains with different APOE genotypes.

Constructing and Pilot Testing a Novel Prostate Magnetic Resonance Imaging/Ultrasound Fusion Biopsy Phantom.

OBJECTIVE: To describe the design and build of a novel phantom for magnetic resonance imaging (MRI)/ultrasound (US) fusion biopsy and present pilot testing results from a multicenter urology resident training session. METHODS: We cast our phantom from polyvinylchloride-plastisol that features 10 mm and 5 mm blue clay tumors, a urethral lumen, and an echogenic capsule. T2-weighted images were acquired with a 3T MR750 scanner (GE Healthcare, Boston, MA). Fusion testing was performed on the bkFusion system (BK ultrasound, Peabody, MA) with MIM Symphony software (MIM, Cleveland, OH) and an 18-gauge Bard Monopty disposable gun (Bard, Murray Hill, NJ). Twenty residents from 6 urology programs in Chicago performed proctored user testing. RESULTS: The per phantom material cost was $12. The phantom was compatible with all necessary equipment to create a MRI/US fusion data set. MRI and US imaging characteristics were excellent with hypointense lesions. Image fusion was achieved through both end and side fire ultrasound probes. The phantom allowed for biopsies to be performed, and target lesion hits were confirmed by visual inspection of core samples. 38% (8/21) of urology resident pilot testing participants had previously performed a fusion biopsy. The mean postsession survey scores were (1-10 [best]): realism 9.0, usefulness 9.4, ease of use 9.1, ease of orientation 8.9, and overall experience 9.3. CONCLUSION: This simple and inexpensive phantom allows for training and accuracy testing of MRI/US fusion biopsy hardware and software platforms.

Improved Differentiation of Low-Grade and High-Grade Gliomas and Detection of Tumor Proliferation Using APT Contrast Fitted from Z-Spectrum.

PURPOSE: The purpose of the study is to demonstrate the value of quantitative amide proton transfer (APT) imaging for differentiating glioma grades and detecting tumor proliferation. PROCEDURES: This study included 32 subjects with 16 low-grade gliomas (LGG) and 16 high-grade gliomas (HGG) confirmed by histopathology. Chemical exchange saturation transfer (CEST) magnetic resonance imaging with APT weighting was performed on a 3 T scanner. After B0 correction, Z-spectra were fitted with Lorentzian functions corresponding to the upfield semi-solid magnetization transfer and nuclear overhauser enhancement (MT&NOE) effect, the direct saturation (DS) effect, and the downfield APT effect centered at around - 1.5, 0, and + 3.5 ppm, respectively. To compute the Z-spectral fitted APT (fitted_APT) in solid tumor tissue, double-peak histogram fitting of pixel MT&NOE effect from the whole tumor was used to remove necrosis regions. The fitted APT was then compared with the conventional APT based on magnetization transfer ratio asymmetry. Receiver operating characteristic (ROC) analysis was used to compare the performance between Z-spectral fitted contrasts and the con_APT for LGG versus HGG differentiation. Additionally, the correlations between the imaging contrasts (fitted_APT, con_APT, and fitted_MT&NOE) and Ki-67 labeling index for tumor proliferation were also evaluated. RESULTS: Z-spectral fitted_APT shows improved statistical power for differentiating HGG and LGG (7.58 ± 0.99 vs. 6.79 ± 1.05 %, p < 0.05) than con_APT (4.34 ± 0.95 vs. 4.05 ± 2.02 %, p > 0.05) in solid tumor tissues. Analyses of whole tumor, on the other hand, have less differentiating power for both fitted_APT (p from 0.032 to 0.08) and con_APT (p from 0.696 to 0.809). Similarly, based on ROC analyses, fitted_APT shows larger area under the curve (AUC = 0.723) than con_APT (AUC = 0.543). The combination of fitted APT, DS, and MT&NOE further improved the specificity (75 %), diagnostic accuracy (78.2 %), and area under the curve (0.758) in differentiating LGG and HGG. Consistently, fitted_APT (r = 0.451, p = 0.018) is better correlated with Ki-67 than con_APT (r = 0.331, p = 0.092). CONCLUSIONS: Fitted APT from Z-spectrum improves differentiation of low- and high-grade gliomas and better correlated with tumor proliferation than conventional APT.

Creatine CEST MRI for Differentiating Gliomas with Different Degrees of Aggressiveness.

PURPOSE: Creatine (Cr) is a major metabolite in the bioenergetic system. Measurement of Cr using conventional MR spectroscopy (MRS) suffers from low spatial resolution and relatively long acquisition times. Creatine chemical exchange saturation transfer (CrCEST) magnetic resonance imaging (MRI) is an emerging molecular imaging method for tissue Cr measurements. Our previous study showed that the CrCEST contrast, obtained through multicomponent Z-spectral fitting, was lower in tumors compared to normal brain, which further reduced with tumor progression. The current study was aimed to investigate if CrCEST MRI can also be useful for differentiating gliomas with different degrees of aggressiveness. PROCEDURES: Intracranial 9L gliosarcoma and F98 glioma bearing rats with matched tumor size were scanned with a 9.4 T MRI scanner at two time points. CEST Z-spectra were collected using a customized sequence with a frequency-selective rectangular saturation pulse (B1 = 50 Hz, duration = 3 s) followed by a single-shot readout. Z spectral data were fitted pixel-wise with five Lorentzian functions, and maps of CrCEST peak amplitude, linewidth, and integral were produced. For comparison, single-voxel proton MR spectroscopy (1H-MRS) was performed to quantify and compare the total Cr concentration in the tumor. RESULTS: CrCEST contrasts decreased with tumor progression from weeks 3 to 4 in both 9L and F98 phenotypes. More importantly, F98 tumors had significantly lower CrCEST integral compared to 9L tumors. On the other hand, integrals of other Z-spectral components were unable to differentiate both tumor progression and phenotype with limited sample size. CONCLUSIONS: Given that F98 is a more aggressive tumor than 9L, this study suggests that CrCEST MRI may help differentiate gliomas with different aggressiveness.

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.

Noninvasive intracranial compliance from MRI-based measurements of transcranial blood and CSF flows: indirect versus direct approach.

Intracranial compliance (ICC) determines the ability of the intracranial compartment to accommodate an increase in volume without a large increase in intracranial pressure (ICP). The clinical utilization of ICC is limited by the invasiveness of current measurement. Several investigators attempted to estimate ICC noninvasively, from magnetic resonance imaging (MRI) measurements of cerebral blood and cerebral spinal fluid flows, either using indirect measures of ICC or directly by measuring the ratio of the changes in intracranial volume and pressure during the cardiac cycle. The indirect measures include the phase lag between the cerebrospinal fluid (CSF) and its driving force, either arterial inflow or net transcranial blood flow. This study compares the sensitivity of phase-based and amplitude-based measures of ICC to changes in ICC. In vivo volumetric blood and CSF flows measured by MRI phase contrast from healthy volunteers and from patients with elevated ICP were used for the comparison. An RLC circuit model of the craniospinal system was utilized to simulate the effect of a change in ICC on the CSF flow waveform. The simulations demonstrated that amplitude-based measures of ICC are considerably more sensitive than phase-based measures, and among the amplitude-based measures, the ICC index provides the most reliable estimate of ICC.

Influence of the compliance of the neck arteries and veins on the measurement of intracranial volume change by phase-contrast MRI.

PURPOSE: To assess the influence of arterial and venous vascular compliances in the neck region on the measurement of the change in intracranial volume during the cardiac cycle. MATERIALS AND METHODS: Arterial and venous blood flows were imaged by MRI phase contrast at two different locations, one close to the skull base (upper) and one 2-3 cm lower, around C3 level (lower). Maximal intracranial volume change (ICVC) measurements were derived from the momentary difference between the arterial inflow and venous outflow rates at the upper and lower locations separately to assess the influence of the compliances of the vessel segments bounded by the two different imaging locations. Imaging location for the craniospinal cerebrospinal fluid flow was a constant variable in this experiment. RESULTS: The systolic ICVC obtained using the lower location was consistently larger than when using the upper location. Comparison between arterial and venous flow dynamics revealed a much larger changes in flow dynamic and lumen areas in the veins compared with the arteries, which explain the large venous influence on the intracranial volume change measurement. CONCLUSION: Arterial inflow and venous outflow should be sampled at a level close to the skull base (C1-C2) to minimize the influence of the compliance of arteries and the collapsibility of veins for a reliable measurement of ICVC.