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.

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.

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.

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.

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.

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.

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.

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.

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.