Magnetization Transfer Pulse Research Articles

Superior lesion detection on 3D FSE T1WI with magnetization transfer and CHESS preparation pulses in children with focal epilepsy: Preliminary results.

In childhood drug-resistant focal epilepsy, the identification of a magnetic resonance imaging lesion significantly affects the management and prognosis, although it is often challenging. Herein we report the preliminary results of a modified MR sequence, in which both magnetization transfer and chemical shift selective preparation pulses are added to a 3D fast spin echo T1-weighted sequence to recognize focal cortical dysplasia. The scan time is short, and the images have expected uniform suppression of the background normal gray and white matter. We report four children with focal epilepsy, in whom the focal cortical and subcortical lesions are superiorly conspicuous on the aforementioned MR sequence compared to the high-resolution fluid-attenuated inversion recovery images obtained with typical epilepsy MR protocols.

Ultra-low-field magnetization transfer imaging at 0.055T with low specific absorption rate.

To demonstrate magnetization transfer (MT) effects with low specific absorption rate (SAR) on ultra-low-field (ULF) MRI. MT imaging was implemented by using sinc-modulated RF pulse train (SPT) modules to provide bilateral off-resonance irradiation. They were incorporated into 3D gradient echo (GRE) and fast spin echo (FSE) protocols on a shielding-free 0.055T head scanner. MT effects were first verified using phantoms. Brain MT imaging was conducted in both healthy subjects and patients. MT effects were clearly observed in phantoms using six SPT modules with total flip angle 3600° at central primary saturation bands of approximate offset ±786 Hz, even in the presence of large relative B0 inhomogeneity. For brain, strong MT effects were observed in gray matter, white matter, and muscle in 3D GRE and FSE imaging using six and sixteen SPT modules with total flip angle 3600° and 9600°, respectively. Fat, cerebrospinal fluid, and blood exhibited relatively weak MT effects. MT preparation enhanced tissue contrasts in T2-weighted and FLAIR-like images, and improved brain lesion delineation. The estimated MT SAR was 0.0024 and 0.0008 W/kg for two protocols, respectively, which is far below the US Food and Drug Administration (FDA) limit of 3.0 W/kg. Robust MT effects can be readily obtained at ULF with extremely low SAR, despite poor relative B0 homogeneity in ppm. This unique advantage enables flexible MT pulse design and implementation on low-cost ULF MRI platforms to achieve strong MT effects in brain and beyond, potentially augmenting their clinical utility in the future.

Comparison of 3D Magnetization-transfer- and Spectral-presaturation-with-inversion-recovery-based Neuromelanin Imaging.

Neuromelanin is visualized by optimizing the conditions of longitudinal relaxation (T1)-weighted imaging (T1WI). Although it was originally developed in 2D imaging, 3D imaging has been also reported, and T1WI sequences with magnetization transfer (MT) pulses are now widely used in 3D gradient echo (GRE) sequences. In this study, we assert that the use of spectral presaturation with inversion recovery (SPIR) may also be useful as an alternative to MT pulses, and we optimize SPIR and compare it with MT. Neuromelanin images with MT pulse and SPIR (flip angles [FAs] = 19º, 22º, and 25º) were acquired from 30 healthy volunteers. To achieve the same acquisition time of 5 min, the slab thickness of the MT images was less than 1/3 of those of the SPIR images; the acquisition areas for MT and SPIR were the brainstem and the whole brain, respectively. Visual and quantitative evaluation was performed and compared on the four sequences acquired for the substantia nigra pars compacta (SNc) and the locus coeruleus (LC). For visual assessment, we used the mean score from a 3-point scale by two evaluators. For quantitative evaluation, the contrast ratios of SNc and LC were calculated in comparison with the background tissue signal. In visual assessments, the mean scores of the SPIR FA19º and FA22º images were better than others in the SNc. Regarding LC, the SPIR FA22º image yielded the best mean score. In quantitative evaluations, the MT image was significantly lower than the other three images in SNc. Regarding LC, there were no significant differences among the four acquired images (MT and SPIR FA19º, FA22º, and FA25º). Detection of neuromelanin in SNc and LC was improved by the use of SPIR compared to MT pulse in 3D neuromelanin imaging.

Amide Proton Transfer-Weighted Imaging and Multiple Models Intravoxel Incoherent Motion-Based 18F-FDG PET/MRI for Predicting Progression-Free Survival in Non-Small Cell Lung Cancer.

Amide proton transfer-weighted imaging (APTWI) and multiple models intravoxel incoherent motion (IVIM) based 18F-FDG PET/MR could reflect the microscopic information of the tumor from multiple perspectives. However, its value in the prognostic assessment of non-small cell lung cancer (NSCLC) still needs to be further explored. To determine whether pretreatment APTWI, mono-, bi-, and stretched-exponential model IVIM, and 18F-FDG PET-derived parameters of the primary lesion may be associated with progression-free survival (PFS) in NSCLC. Prospective. Seventy-seven patients (mean age, 62 years, range, 20-81 years) with 37 men and 40 women were included. 3.0 T 18F-FDG PET/MRI, single shot echo planar imaging sequences for IVIM and fast spin-echo sequences with magnetization transfer pulses for APTWI. Patient clinical characteristics (age, sex, smoke, subtype, TNM stage, and surgery), PFS (chest CT every 3 months, median follow-up was 18 months, range, 4-27 months), and APTWI (MTRasym(3.5 ppm)), IVIM (ADCstand, D, D*, f, DDC, and α), and 18F-FDG PET (SUVmax, MTV, and TLG) parameters were recorded. Proportional hazards model, concordance index, calibration curve, decision curve analysis (DCA), and Log-rank test. A P value <0.05 was considered statistically significant. Histological subtype, TNM stage, MTV, D*, and MTRasym(3.5 ppm) were all independent predictors of PFS. A prediction model based on these predictors was developed with a C-index of 0.895 (95% CI: 0.839-0.951), which was significantly superior to each of the above predictors alone (C-index = 0.629, 0.707, 0.692, 0.678, and 0.558, respectively). The calibration curve and DCA indicated good consistency and clinical utility of the prediction model, respectively. Log-rank test results showed a significant difference in PFS between the high- and low-risk groups. APTWI and multiple models IVIM based 18F-FDG PET/MRI can be used for PFS assessment in NSCLC. 3 TECHNICAL EFFICACY: Stage 2.

Chemical Exchange Saturation Transfer MRI: Capability for Predicting Therapeutic Effect of Chemoradiotherapy on Non-Small Cell Lung Cancer Patients.

Amide proton transfer (APT) weighted chemical exchange saturation transfer CEST (APTw/CEST) magnetic resonance imaging (MRI) has been suggested as having the potential for assessing the therapeutic effect of brain tumors or rectal cancer. Moreover, diffusion-weighted imaging (DWI) and positron emission tomography fused with computed tomography by means of 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG-PET/CT) have been suggested as useful in same setting. To compare the capability of APTw/CEST imaging, DWI, and FDG-PET/CT for predicting therapeutic effect of chemoradiotherapy (CRT) on stage III non-small cell lung cancer (NSCLC) patients. Prospective. Eighty-four consecutive patients with Stage III NSCLC, 45 men (age range, 62-75 years; mean age, 71 years) and 39 women (age range, 57-75 years; mean age, 70 years). All patients were then divided into two groups (Response Evaluation Criteria in Solid Tumors [RECIST] responders, consisting of the complete response and partial response groups, and RECIST non-responders, consisting of the stable disease and progressive disease groups). 3 T, echo planar imaging or fast advanced spin-echo (FASE) sequences for DWI and 2D half Fourier FASE sequences with magnetization transfer pulses for CEST imaging. Magnetization transfer ratio asymmetry (MTRasym ) at 3.5 ppm, apparent diffusion coefficient (ADC), and maximum standard uptake value (SUVmax, ) on PET/CT were assessed by means of region of interest (ROI) measurements at primary tumor. Kaplan-Meier method followed by log-rank test and Cox proportional hazards regression analysis with multivariate analysis. A P value <0.05 was considered statistically significant. Progression-free survival (PFS) and overall survival (OS) had significant difference between two groups. MTRasym at 3.5 ppm (hazard ratio [HR] = 0.70) and SUVmax (HR = 1.41) were identified as significant predictors for PFS. Tumor staging (HR = 0.57) was also significant predictors for OS. APTw/CEST imaging showed potential performance as DWI and FDG-PET/CT for predicting the therapeutic effect of CRT on stage III NSCLC patients. 2 TECHNICAL EFFICACY: Stage 1.

Acceleration of neuromelanin-sensitive MRI sequences in the substantia nigra using standard MRI options

PurposeNeuromelanin MRI (NM-MRI) is applied as a proxy measurement of dopaminergic functioning of the substantia nigra pars compacta (SN). To increase its clinical applicability, a fast and easily applicable NM-MRI sequence is needed. This study therefore compared accelerated NM-MRI sequences using standard available MRI options with a validated 2D gradient recalled echo NM-MRI sequence with off-resonance magnetization transfer (MT) pulse (2D-MToffRes).MethodsWe used different combinations of compressed sense (CS) acceleration, repetition times (TR), and MT pulse to accelerate the validated 2D-MToffRes. In addition, we compared a recently introduced 3D sequence with the 2D-MToffRes.ResultsOur results show that the 2D sequences perform best with good to excellent reliability. Only excellent intraclass correlation coefficients were found for the CS factor 2 sequences.ConclusionWe conclude that there are several reliable approaches to accelerate NM-MRI, in particular by using CS.

7-T Neuromelanin and R2* MRI in Parkinson Disease.

HomeRadiologyVol. 305, No. 2 PreviousNext Reviews and CommentaryFree AccessImages in Radiology7-T Neuromelanin and R2* MRI in Parkinson DiseaseDhairya A. Lakhani, Erik H. Middlebrooks Dhairya A. Lakhani, Erik H. Middlebrooks Author AffiliationsFrom the Department of Radiology, West Virginia University, Morgantown, W.Va. (D.A.L.); and Department of Radiology, Mayo Clinic College of Medicine and Science, 4500 San Pablo Rd, Jacksonville, FL 32224 (E.H.M.).Address correspondence to E.H.M. (email: [email protected]).Dhairya A. LakhaniErik H. Middlebrooks Published Online:Aug 2 2022https://doi.org/10.1148/radiol.220230MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In A 76-year-old man presented with worsening balance, shuffling gait, and right-hand tremor, beginning 3 years before evaluation. On examination, he had reduced facial expressions, reduced blink rate, and hypophonic voice. His gait was slow and shuffling, with bilateral reduced arm swing. He also had rigidity and bradykinesia in all four extremities, greater on the right. His examination features were typical of the akinetic-rigid subtype of Parkinson disease (PD). He underwent brain MRI to support the diagnosis and to assess for other etiologies, such as an atypical parkinsonian syndrome.In this case, we used a high-spatial-resolution multiecho gradient-echo sequence with magnetization transfer pulse at 7 T to image neuromelanin in the substantia nigra, which normally has a high concentration of neuromelanin-rich cells. Neuromelanin imaging stands to benefit from 7-T MRI due to higher signal-to-noise ratio, tissue contrast, and spatial resolution. Reduced size and signal intensity of the substantia nigra were consistent with PD (Figure). Additionally, the multiecho sequence allowed for the quantification of the R2*, which reveals elevated iron deposition in this case, another histopathologic feature of PD (Figure). The combination of both biomarkers has potential to be a powerful tool for diagnosis and monitoring progression of PD.Images in a 76-year-old man with akinetic-rigid subtype Parkinson disease (PD) with symptoms greater on the right side. (A) Axial neuromelanin-sensitive MRI scan derived from rigid subtype PD shows reduced size and signal intensity of the substantia nigra (SN) (arrows) on the first echo image of a neuromelanin-sensitive three-dimensional multiecho fast low-angle shot, or FLASH, MRI scan with magnetization transfer pulse (7-T Siemens MAGNETOM Terra [Siemens Healthineers]; repetition time, 52 m/sec; echo time, 2.18, 4.15, and 7.09 m/sec; section thickness, 1.5 mm; flip angle, 16°; averages, 1; interpolated voxel size, 0.4 × 0.4 × 1.5 mm; acquisition time, 10 minutes and19 seconds). (B) MRI scan in a 73-year-old woman with the diagnosis of essential tremor is shown for illustration of the normal appearance of the substantia nigra (arrows) as comparison. (C) Plot graph of the substantia-nigra signal intensity (normalized by the adjacent cerebral-peduncle signal intensity) over the three echoes shows decreased neuromelanin in the patient with PD (greater decrease in the left substantia nigra) on the first echo neuromelanin-sensitive image. There is also a more rapid decrease in signal intensity over the second and third echoes, reflecting increased R2* effect from elevated iron deposition.Download as PowerPointOpen in Image Viewer Disclosures of conflicts of interest: D.A.L. No relevant relationships. E.H.M. Clinical trial and research funding paid to institution by Varian Medical Systems and Boston Scientific; unrelated consultant fees from Boston Scientific.Article HistoryReceived: Feb 1 2022Revision requested: Mar 7 2022Revision received: Mar 15 2022Accepted: Mar 18 2022Published online: Aug 02 2022Published in print: Nov 2022 FiguresReferencesRelatedDetailsRecommended Articles Substantia Nigra Volumetry with 3-T MRI in De Novo and Advanced Parkinson DiseaseRadiology2020Volume: 296Issue: 2pp. 401-410Differential Effect of Iron and Myelin on Susceptibility MRI in the Substantia NigraRadiology2021Volume: 301Issue: 3pp. 682-691High-Spatial-Resolution Diffusion MRI in Parkinson Disease: Lateral Asymmetry of the Substantia NigraRadiology2019Volume: 291Issue: 1pp. 149-157Imaging the Substantia Nigra in Parkinson Disease and Other Parkinsonian SyndromesRadiology2021Volume: 300Issue: 2pp. 260-278Is High-Spatial-Resolution Diffusion MRI Applicable for the Diagnosis of Parkinson Disease?Radiology2019Volume: 292Issue: 1pp. 267-268See More RSNA Education Exhibits Parkinsonian Syndromes: The Past, Present, and FutureDigital Posters2019Contemporary MRI Imaging in Parkinson's DiseaseDigital Posters2019The Role of MR-guided Focused Ultrasound as a Symptomatic Treatment for Parkinson's Disease: Behind and BeyondDigital Posters2020 RSNA Case Collection Primary HemochromatosisRSNA Case Collection2021NeuroferritinopathyRSNA Case Collection2021Multiple System Atrophy (MSA)RSNA Case Collection2021 Vol. 305, No. 2 Metrics Altmetric Score PDF download

Evaluating the Cisplatin Dose Dependence of Testicular Dysfunction Using Creatine Chemical Exchange Saturation Transfer Imaging.

Chemical exchange saturation transfer (CEST) imaging is a non-invasive molecular imaging technique for indirectly measuring low-concentration endogenous metabolites. Conventional CEST has low specificity, owing to the effects of spillover, magnetization transfer (MT), and T1 relaxation, thus necessitating an inverse Z-spectrum analysis. We aimed to investigate the usefulness of inverse Z-spectrum analysis in creatine (Cr)-CEST in mice, by conducting preclinical 7T-magnetic resonance imaging (MRI) and comparing the conventional analysis metric magnetization transfer ratio (MTRconv) with the novel metric apparent exchange-dependent relaxation (AREX). We performed Cr-CEST imaging using 7T-MRI on mouse testes, using C57BL/6 mice as the control and a cisplatin-treated model. We prepared different doses of cisplatin to observe its dose dependence effect on testicular function. CEST imaging was obtained using an MT pulse with varying saturation frequencies, ranging from −4.8 ppm to +4.8 ppm. The application of control mouse testes improved the specificity of the CEST effect and image contrast between the testes and testicular epithelium. The cisplatin-treated model revealed impaired testicular function, and the Cr-CEST imaging displayed decreased Cr levels in the testes. There was a significant difference between the low- and high-dose models. The MTR values of Cr-CEST reflected the cisplatin dose dependence of testicular dysfunction.

Generalized Bloch model: A theory for pulsed magnetization transfer.

The paper introduces a classical model to describe the dynamics of large spin-1/2 ensembles associated with nuclei bound in large molecule structures, commonly referred to as the semi-solid spin pool, and their magnetization transfer (MT) to spins of nuclei in water. Like quantum-mechanical descriptions of spin dynamics and like the original Bloch equations, but unlike existing MT models, the proposed model is based on the algebra of angular momentum in the sense that it explicitly models the rotations induced by radiofrequency (RF) pulses. It generalizes the original Bloch model to non-exponential decays, which are, for example, observed for semi-solid spin pools. The combination of rotations with non-exponential decays is facilitated by describing the latter as Green's functions, comprised in an integro-differential equation. Our model describes the data of an inversion-recovery magnetization-transfer experiment with varying durations of the inversion pulse substantially better than established models. We made this observation for all measured data, but in particular for pulse durations smaller than 300μs. Furthermore, we provide a linear approximation of the generalized Bloch model that reduces the simulation time by approximately a factor 15,000, enabling simulation of the spin dynamics caused by a rectangular RF-pulse in roughly 2μs. The proposed theory unifies the original Bloch model, Henkelman's steady-state theory for MT, and the commonly assumed rotation induced by hard pulses (i.e., strong and infinitesimally short applications of RF-fields) and describes experimental data better than previous models.

Cross-Scanner Harmonization of Neuromelanin-Sensitive MRI for Multisite Studies.

Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) is a validated measure of neuromelanin concentration in the substantia nigra-ventral tegmental area (SN-VTA) complex and is a proxy measure of dopaminergic function with potential as a noninvasive biomarker. The development of generalizable biomarkers requires large-scale samples necessitating harmonization approaches to combine data collected across sites. To develop a method to harmonize NM-MRI across scanners and sites. Prospective. A total of 128 healthy subjects (18-73 years old; 45% female) from three sites and five MRI scanners. 3.0 T; NM-MRI two-dimensional gradient-recalled echo with magnetization-transfer pulse and three-dimensional T1-weighted images. NM-MRI contrast (contrast-to-noise ratio [CNR]) maps were calculated and CNR values within the SN-VTA (defined previously by manual tracing on a standardized NM-MRI template) were determined before harmonization (raw CNR) and after ComBat harmonization (harmonized CNR). Scanner differences were assessed by calculating the classification accuracy of a support vector machine (SVM). To assess the effect of harmonization on biological variability, support vector regression (SVR) was used to predict age and the difference in goodness-of-fit (Δr) was calculated as the correlation (between actual and predicted ages) for the harmonized CNR minus the correlation for the raw CNR. Permutation tests were used to determine if SVM classification accuracy was above chance level and if SVR Δr was significant. A P-value <0.05 was considered significant. In the raw CNR, SVM MRI scanner classification was above chance level (accuracy=86.5%). In the harmonized CNR, the accuracy of the SVM was at chance level (accuracy=29.5%; P=0.8542). There was no significant difference in age prediction using the raw or harmonized CNR (Δr=-0.06; P=0.7304). ComBat harmonization removes differences in SN-VTA CNR across scanners while preserving biologically meaningful variability associated with age. 2 TECHNICAL EFFICACY: 1.

Reliability and Reproducibility of Neuromelanin-Sensitive Imaging of the Substantia Nigra: A Comparison of Three Different Sequences.

BackgroundNeuromelanin‐sensitive MRI (NM‐MRI) of the substantia nigra provides a noninvasive way to acquire an indirect measure of dopamine functioning. Despite the potential of NM‐MRI as a candidate biomarker for dopaminergic pathology, studies about its reproducibility are sparse.PurposeTo assess the test–retest reproducibility of three commonly used NM‐MRI sequences and evaluate three analysis methods.Study TypeProspective study.PopulationA total of 11 healthy participants age between 20–27 years.Field Strength/Sequence3.0T; NM‐MRI gradient recalled echo (GRE) with magnetization transfer (MT) pulse; NM‐MRI turbo spin echo (TSE) with MT pulse; NM‐MRI TSE without MT pulse.AssessmentParticipants were scanned twice with a 3‐week interval. Manual analysis, threshold analysis, and voxelwise analysis were performed for volume and contrast ratio (CR) measurements.Statistical TestsIntraclass correlation coefficients (ICCs) were calculated for test–retest and inter‐ and intrarater variability.ResultsThe GRE sequence achieved the highest contrast and lowest variability (4.9–5.7%) and showed substantial to almost perfect test–retest ICC (0.72–0.90) for CR measurements. For volume measurements, the manual analysis showed a higher variability (10.7–17.9%) and scored lower test–retest ICCs (–0.13–0.73) than the other analysis methods. The threshold analysis showed higher test–retest ICC (0.77) than the manual analysis for the volume measurements.Data ConclusionNM‐MRI is a highly reproducible measure, especially when using the GRE sequence and CR measurements. Volume measurements appear to be more sensitive to inter/intrarater variability and variability in placement and orientation of the NM‐MRI slab. The threshold analysis appears to be the best alternative for volume analysis.Level of Evidence2Technical Efficacy Stage1

Age-related decrease in collagen proton fraction in tibial tendons estimated by magnetization transfer modeling of ultrashort echo time magnetic resonance imaging (UTE-MRI)

Clinical magnetic resonance imaging (MRI) sequences are not often capable of directly visualizing tendons. Ultrashort echo time (UTE) MRI can acquire high signal from tendons thus enabling quantitative assessments. Magnetization transfer (MT) modeling combined with UTE-MRI—UTE-MT-modeling—can indirectly assess macromolecular protons in the tendon. This study aimed to determine if UTE-MT-modeling is a quantitative technique sensitive to the age-related changes of tendons. The legs of 26 young healthy (29 ± 6 years old) and 22 elderly (75 ± 8 years old) female subjects were imaged using UTE sequences on a 3T MRI scanner. Institutional review board approval was obtained, and all recruited subjects provided written informed consent. T1 and UTE-MT-modeling were performed on anterior tibialis tendons (ATT) and posterior tibialis tendons (PTT) as two representative human leg tendons. A series of MT pulse saturation powers (500–1500°) and frequency offsets (2–50 kHz) were used to measure the macromolecular fraction (MMF) and macromolecular T2 (T2MM). All measurements were repeated by three independent readers for a reproducibility study. MMF demonstrated significantly lower values on average in the elderly cohort compared with the younger cohort for both ATT (decreased by 16.8%, p = 0.03) and PTT (decreased by 23.0%, p < 0.01). T2MM and T1 did not show a significant nor a consistent difference between the young and elderly cohorts. For all MRI parameters, intraclass correlation coefficient (ICC) was higher than 0.98, indicating excellent consistency between measurements performed by independent readers. MMF serving as a surrogate measure for collagen content, showed a significant decrease in elderly leg tendons. This study highlighted UTE-MRI-MT techniques as a useful quantitative method to assess the impact of aging on human tendons.

Assessing cortical bone mechanical properties using collagen proton fraction from ultrashort echo time magnetization transfer (UTE-MT) MRI modeling

Cortical bone shows as a signal void when using conventional clinical magnetic resonance imaging (MRI). Ultrashort echo time MRI (UTE-MRI) can acquire high signal from cortical bone, thus enabling quantitative assessments. Magnetization transfer (MT) imaging combined with UTE-MRI can indirectly assess protons in the organic matrix of bone. This study aimed to examine UTE-MT MRI techniques to estimate the mechanical properties of cortical bone. A total of 156 rectangular human cortical bone strips were harvested from the tibial and femoral midshafts of 43 donors (62 ± 22 years old, 62 specimens from females, 94 specimens from males). Bone specimens were scanned using UTE-MT sequences on a clinical 3 T MRI scanner and on a micro-computed tomography (μCT) scanner. A series of MT pulse saturation powers (400°, 600°, 800°) and frequency offsets (2, 5, 10, 20, 50 kHz) was used to measure the macromolecular fraction (MMF) utilizing a two-pool MT model. Failure mechanical properties of the bone specimens were measured using 4-point bending tests. MMF from MRI results showed significant strong correlations with cortical bone porosity (R = -0.72, P < 0.01) and bone mineral density (BMD) (R = +0.71, P < 0.01). MMF demonstrated significant moderate correlations with Young modulus, yield stress, and ultimate stress (R = 0.60–0.61, P < 0.01). These results suggest that the two-pool UTE-MT model focusing on the organic matrix of bone can potentially serve as a novel tool to detect the variations of bone mechanical properties and intracortical porosity.

Amide proton transfer imaging of glioblastoma, neuroblastoma, and breast cancer cells on a 11.7 T magnetic resonance imaging system

PurposeThe purpose of this study was (i) to determine the optimal magnetization transfer (MT) pulse parameter for amide proton transfer (APT) chemical exchange saturation transfer (CEST) imaging on an ultra-high-field magnetic resonance imaging (MRI) system and (ii) to use APT CEST imaging to noninvasively assess brain orthotopic and ectopic tumor cells transplanted into the mouse brain. MethodsTo evaluate APT without the influence of other metabolites, we prepared egg white phantoms. Next, we used 7–11-week-old nude female mice and the following cell lines to establish tumors after injection into the left striatum of mice: C6 (rat glioma, n = 8) as primary tumors and Neuro-2A (mouse neuroblastoma, n = 11) and MDA-MB231 (human breast cancer, n = 8) as metastatic tumors. All MRI experiments were performed on an 11.7 T vertical-bore scanner. CEST imaging was performed at 1 week after injection of Neuro-2A cells and at 2 weeks after injection of C6 and MDA-MB231 cells. The MT pulse amplitude was set at 2.2 μT or 4.4 μT. We calculated and compared the magnetization transfer ratio (MTR) and difference of MTR asymmetry between normal tissue and tumor (ΔMTR asymmetry) on APT CEST images between mouse models of brain tumors. Then, we performed hematoxylin and eosin (HE) staining and Ki-67 immunohistochemical staining to compare the APT CEST effect on tumor tissues and the pathological findings. ResultsPhantom study of the amide proton phantom containing chicken egg white, z-spectra obtained at a pulse length of 500 ms showed smaller peaks, whereas those obtained at a pulse length of 2000 ms showed slightly higher peaks. The APT CEST effect on tumor tissues was clearer at a pulse amplitude of 2.2 μT than at 4.4 μT. For all mouse models of brain tumors, ΔMTR asymmetry was higher at 2.2 μT than at 4.4 μT. ΔMTR asymmetry was significantly higher for the Neuro-2A model than for the MDA-MB231 model. HE staining revealed light bleeding in Neuro-2A tumors. Immunohistochemical staining revealed that the density of Ki-67-positive cells was higher in Neuro-2A tumors than in C6 or MDA-MB231 tumors. ConclusionThe MTR was higher at 4.4 μT than at 2.2 μT for each concentration of egg white at a pulse length of 500 ms or 2000 ms. High-resolution APT CEST imaging on an ultra-high-field MRI system was able to provide tumor information such as proliferative potential and intratumoral bleeding, noninvasively.

Gadolinium-Enhanced Susceptibility-Weighted Imaging in Multiple Sclerosis: Optimizing the Recognition of Active Plaques for Different MR Imaging Sequences.

Gadolinium SWI is MR imaging that has recently been reported to be effective in the evaluation of several neurologic disorders, including demyelinating diseases. Our aim was to analyze the accuracy of gadolinium SWI for detecting the imaging evidence of active inflammation on MS plaques when a BBB dysfunction is demonstrated by a focal gadolinium-enhanced lesion and to compare this technique with gadolinium-enhanced T1 spin-echo and T1 spin-echo with magnetization transfer contrast. MR imaging studies of 103 patients (170 examinations) were performed using a 1.5T scanner. Two neuroradiologists scrutinized signal abnormalities of the demyelinating plaques on gadolinium SWI and compared them with gadolinium T1 before and after an additional magnetization transfer pulse. Interrater agreement was evaluated among gadolinium T1 magnetization transfer contrast, gadolinium SWI, and gadolinium T1 spin-echo using the κ coefficient. The T1 magnetization transfer contrast sequence was adopted as the criterion standard in this cohort. Thus, the sensitivity, specificity, positive predictive value, and negative predictive value were calculated for gadolinium T1 spin-echo and gadolinium SWI sequences. Differences in BBB dysfunction were evident among gadolinium SWI, gadolinium T1 spin-echo, and gadolinium T1 magnetization transfer contrast. Gadolinium T1 magnetization transfer contrast demonstrated the highest number of active demyelinating plaques. Gadolinium SWI was highly correlated with gadolinium T1 magnetization transfer contrast in depicting acute demyelinating plaques (κ coefficient = 0.860; sensitivity = 0.837), and these techniques provided better performance compared with gadolinium T1 spin-echo (κ coefficient = 0.78; sensitivity = 0.645). Gadolinium SWI was able to better detect BBB dysfunction in MS plaques and had a better performance than gadolinium T1 spin-echo. Increasing SWI sequence applications in clinical practice can improve our knowledge of MS, likely allowing the addition of BBB dysfunction analysis to the striking findings of the previously reported central vein sign.

Magnetization transfer saturation imaging of human calf muscle: Reproducibility and sensitivity to regional and sex differences.

Magnetization transfer saturation (MTsat ) derives a semiquantitative index of magnetization transfer in faster acquisition times than quantitative magnetization transfer; the potential of MTsat for muscle imaging has not yet been explored. To evaluate the potential of MTsat to identify regional and sex differences in calf muscle. Prospective cohort study. Vials with different agar and nickel nitrate concentrations providing a range of macromolecular fraction and T1 . Seven male subjects (25 ± 7 years) and seven female subjects (28 ± 14 years); three subjects were scanned in three separate sessions to assess reproducibility. 3T, 3D fast low angle shot (FLASH) sequence with and without a magnetization transfer pulse; acquisition time of 4.12 minutes. The effectiveness of two methods of fat suppression was evaluated using the fat unsuppressed sequence as the reference and MTsat maps derived with and without transmit field inhomogeneity corrections were compared. Statistical evaluation of MTsat differences between calf muscles and between male and female cohorts was made. Bland-Altman plots were used to assess fat suppression and B1+ correction. The coefficient of variation (CV) and the repeatability coefficient (RC) were calculated from the repeat sessions. Sex and regional differences were assessed using two-way factorial analyses of variance (ANOVAs) with Bonferroni-adjusted independent sample t-tests for post-hoc analyses. In phantoms, MTsat increased linearly with agar concentration and MTsat was independent of T1 (P = 0.229) evaluated in phantoms with two T1 s. The CV and RC of MTsat ranged between 2.65 to 5.03% and 0.13 to 0.38, respectively, in the different calf muscles. MTsat of the tibialis anterior was significantly higher than other muscles (P < 0.05). MTsat in male subjects was significantly higher than in female subjects (P = 0.009). MTsat maps of calf muscle acquired under 5 minutes may have the potential to detect regional and sex differences. 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1227-1237.

Collagen proton fraction from ultrashort echo time magnetization transfer (UTE-MT) MRI modelling correlates significantly with cortical bone porosity measured with micro-computed tomography (μCT).

Intracortical bone porosity is a key microstructural parameter that determines bone mechanical properties. While clinical MRI visualizes the cortical bone with a signal void, ultrashort echo time (UTE) MRI can acquire high signal from cortical bone, thus enabling quantitative assessments. Magnetization transfer (MT) imaging combined with UTE-MRI can indirectly assess protons in the bone collagenous matrix, which are inversely related to porosity. This study aimed to examine UTE-MT MRI techniques to evaluate intracortical bone porosity. Eighteen human cortical bone specimens from the tibial and fibular midshafts were scanned using UTE-MT sequences on a clinical 3T MRI scanner and on a high-resolution micro-computed tomography (μCT) scanner. A series of MT pulse saturation powers (500°, 1000°, 1500°) and frequency offsets (2, 5, 10, 20, 50kHz) were used to measure the macromolecular fraction (MMF) and macromolecular T2 (T2MM ) using a two-pool MT model. The measurements were made on 136 different regions of interest (ROIs). ROIs were selected at three cortical bone layers (from endosteum to periosteum) and four anatomical sites (anterior, mid-medial, mid-lateral, and posterior) to provide a wide range of porosity. MMF showed moderate to strong correlations with intracortical bone porosity (R=-0.67 to -0.73, p<0.01) and bone mineral density (BMD) (R=+0.46 to +0.70, p<0.01). Comparing the average MMF between cortical bone layers revealed a significant increase from the endosteum towards the periosteum. Such a pattern was in agreement with porosity reduction and BMD increase towards the periosteum. These results suggest that the two-pool UTE-MT technique can potentially serve as a novel and accurate tool to assess intracortical bone porosity.

Early detection of elevated lactate levels in a mitochondrial disease model using chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) at 7T-MRI.

This study aimed to use chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) at 7T-MRI for early detection of intracerebral lactate in a mitochondrial disease model without brain lesions. We considered Ndufs4-knockout (KO) mice as Leigh syndrome models and wild-type (WT) mice as control mice. Brain MRI and 1H-MRS were performed. T2WI data acquired with the Rapid Acquisition with Refocused Echoes (RARE) sequence were used for evaluation of brain lesions. CEST imaging of mice brains was performed using RARE with a magnetization transfer (MT) pulse. The MT ratio (MTR) asymmetry curves and five MTR asymmetry maps at 0.5, 1.0, 2.0, 3.0, and 3.5ppm were calculated using these CEST images. Metabolite concentrations were measured by MRS. T2WI MRI revealed no obvious abnormal findings in KO and WT mice brains at 6 weeks of age. The MTR asymmetry maps at 0.5ppm, 1.0ppm, and 2.0ppm of the KO mice were higher than those of the control mice. Brain 1H MRS revealed a significant increase in lactate levels in all KO mice in comparison with those in the control mice. Additionally, creatine levels in the KO mice were slightly higher than those in the control mice. The levels of the other four metabolites-mIns, NAA + NAAG, GPC + PCh, and Glu + Gln-did not change significantly. We propose that CEST imaging can be used as a biomarker of intracerebral elevated lactate levels in mitochondrial disease.

Extended phase graph formalism for systems with magnetization transfer and exchange.

PurposeAn extended phase graph framework (EPG‐X) for modeling systems with exchange or magnetization transfer (MT) is proposed.TheoryEPG‐X models coupled two‐compartment systems by describing each compartment with separate phase graphs that exchange during evolution periods. There are two variants: EPG‐X(BM) for systems governed by the Bloch‐McConnell equations, and EPG‐X(MT) for the pulsed MT formalism. For the MT case, the “bound” protons have no transverse components, so their phase graph consists of only longitudinal states.MethodsThe EPG‐X model was validated against steady‐state solutions and isochromat‐based simulation of gradient‐echo sequences. Three additional test cases were investigated: (i) MT effects in multislice turbo spin‐echo; (ii) variable flip angle gradient‐echo imaging of the type used for MR fingerprinting; and (iii) water exchange in multi‐echo spin‐echo T2 relaxometry.ResultsEPG‐X was validated successfully against isochromat based transient simulations and known steady‐state solutions. EPG‐X(MT) simulations matched in‐vivo measurements of signal attenuation in white matter in multislice turbo spin‐echo images. Magnetic resonance fingerprinting–style experiments with a bovine serum albumin (MT) phantom showed that the data were not consistent with a single‐pool model, but EPG‐X(MT) could be used to fit the data well. The EPG‐X(BM) simulations of multi‐echo spin‐echo T2 relaxometry suggest that exchange could lead to an underestimation of the myelin‐water fraction.ConclusionsThe EPG‐X framework can be used for modeling both steady‐state and transient signal response of systems exhibiting exchange or MT. This may be particularly beneficial for relaxometry approaches that rely on characterizing transient rather than steady‐state sequences. Magn Reson Med 80:767–779, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

B1 Power Optimization for Chemical Exchange Saturation Transfer Imaging: A Phantom Study Using Egg White for Amide Proton Transfer Imaging Applications in the Human Brain.

The chemical exchange saturation transfer (CEST) effect on an egg white (EW) suspension was investigated for optimization of magnetization transfer (MT) power (B1,rms) and pH dependency with the addition of lactic acid. Applying a higher MT pulse, B1,rms, Z-spectrum shows higher asymmetry and the magnetisation transfer ratio (MTR)asym signal increases to around 1–3.5 ppm, indicating a higher CEST effect. Amide proton transfer (APT) at 3.5 ppm shows a signal elevation in MTRasym with the application of higher B1,rms power and high pH. In addition, the hydroxyl proton signal in MTRasym increases as pH is reduced by lactic acid. In Z-spectrum of B1,rms at 1.0 μT and 2.0 μT, the dependence on CEST effect of amide proton and hydroxyl proton could be observed by using an EW suspension phantom. The CEST MT power was optimized on the EW suspension phantom with pH dependency and further confirmed on volunteers. In addition, APT imaging at 3.5 ppm using B1,rms at 1.0 μT performed on two human brains with different pathophysiological conditions indicated appropriate ATP effect.