Off-resonance Saturation Research Articles

Advances in diffuse glioma assessment: preoperative and postoperative applications of chemical exchange saturation transfer.

Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most well-established. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS).

Design and development of a novel flexible ultra-short echo time (FUSE) sequence.

To present the validation of a new Flexible Ultra-Short Echo time (FUSE) pulse sequence using a short-T2 phantom. FUSE was developed to include a range of RF excitation pulses, trajectories, dimensionalities, and long-T2 suppression techniques, enabling real-time interchangeability of acquisition parameters. Additionally, we developed an improved 3D deblurring algorithm to correct for off-resonance artifacts. Several experiments were conducted to validate the efficacy of FUSE, by comparing different approaches for off-resonance artifact correction, variations in RF pulse and trajectory combinations, and long-T2 suppression techniques. All scans were performed on a 3 T system using an in-house short-T2 phantom. The evaluation of results included qualitative comparisons and quantitative assessments of the SNR and contrast-to-noise ratio. Using the capabilities of FUSE, we demonstrated that we could combine a shorter readout duration with our improved deblurring algorithm to effectively reduce off-resonance artifacts. Among the different RF and trajectory combinations, the spiral trajectory with the regular half-inc pulse achieves the highest SNRs. The dual-echo subtraction technique delivers better short-T2 contrast and superior suppression of water and agar signals, whereas the off-resonance saturation method successfully suppresses water and lipid signals simultaneously. In this work, we have validated the use of our new FUSE sequence using a short T2 phantom, demonstrating that multiple UTE acquisitions can be achieved within a single sequence. This new sequence may be useful for acquiring improved UTE images and the development of UTE imaging protocols.

Peripheral nerve involvement in hereditary spastic paraplegia characterized by quantitative magnetic resonance neurography.

Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders. While peripheral nerve involvement is frequent in spastic paraplegia 7 (SPG7), the evidence of peripheral nerve involvement in SPG4 is more controversial. We aimed to characterize lower extremity peripheral nerve involvement in SPG4 and SPG7 by quantitative magnetic resonance neurography (MRN). Twenty-six HSP patients carrying either the SPG4 or SPG7 mutation and 26 age-/sex-matched healthy controls prospectively underwent high-resolution MRN with large coverage of the sciatic and tibial nerve. Dual-echo turbo-spin-echo sequences with spectral fat-saturation were utilized for T2-relaxometry and morphometric quantification, while two gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse were applied for magnetization transfer contrast (MTC) imaging. HSP patients additionally underwent detailed neurologic and electroneurographic assessments. All microstructural (proton spin density [ρ], T2-relaxation time, magnetization transfer ratio) and morphometric (cross-sectional area) quantitative MRN markers were decreased in SPG4 and SPG7 indicating chronic axonopathy. ρ was superior in differentiating subgroups and identifying subclinical nerve damage in SPG4 and SPG7 without neurophysiologic signs of polyneuropathy. MRN markers correlated well with clinical scores and electroneurographic results. MRN characterizes peripheral nerve involvement in SPG4 and SPG7 as a neuropathy with predominant axonal loss. Evidence of peripheral nerve involvement in SPG4 and SPG7, even without electroneurographically manifest polyneuropathy, and the good correlation of MRN markers with clinical measures of disease progression, challenge the traditional view of the existence of HSPs with isolated pyramidal signs and suggest MRN markers as potential progression biomarkers in HSP.

-correction of magnetization transfer saturation maps optimized for 7T postmortem MRI of the brain.

Magnetization transfer saturation ( ) is a useful marker to probe tissue macromolecular content and myelination in the brain. The increased -inhomogeneity at T and significantly larger saturation pulse flip angles which are often used for postmortem studies exceed the limits where previous correction methods are applicable. Here, we develop a calibration-based correction model and procedure, and validate and evaluate it in postmortem 7T data of whole chimpanzee brains. The dependence of was investigated by varying the off-resonance saturation pulse flip angle. For the range of saturation pulse flip angles applied in typical experiments on postmortem tissue, the dependence was close to linear. A linear model with a single calibration constant is proposed to correct bias in by mapping it to the reference value of the saturation pulse flip angle. was estimated voxel-wise in five postmortem chimpanzee brains. "Individual-based global parameters" were obtained by calculating the mean within individual specimen brains and "group-based global parameters" by calculating the means of the individual-based global parameters across the five brains. The linear calibration model described the data well, though was not entirely independent of the underlying tissue and . Individual-based correction parameters and a group-based global correction parameter ( ) led to visible, quantifiable reductions of -biases in high-resolution maps. The presented model and calibration approach effectively corrects for inhomogeneities in postmortem 7T data.

Quantitative magnetic resonance neurographic characterization of peripheral nerve involvement in manifest and pre-ataxic spinocerebellar ataxia type 3.

Knowledge about the exact underlying pathophysiological changes involved in the genesis and progression of spinocerebellar ataxia type 3 (SCA3) is limited. Lower extremity peripheral nerve lesions in clinically, genetically and electrophysiologically classified ataxic and pre-ataxic SCA3mutation carriers were characterized and quantified by magnetic resonance neurography (MRN). Eighteen SCA3mutation carriers and 20 age-/sex-matched healthy controls were prospectively enrolled. All SCA3mutation carriers underwent detailed neurological and electrophysiological examinations. 3 T MRN covered the lumbosacral plexus and proximal thigh to the tibiotalar joint by using T2-weighted inversion recovery sequences, dual-echo relaxometry sequences with spectral fat saturation, and two gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse. Detailed quantification of nerve lesions by morphometric and microstructural MRN markers, including T2 relaxometry and magnetization transfer contrast imaging, was conducted in all study participants. MRN detected peripheral nerve damage in ataxic and pre-ataxic SCA3. The quantitative markers proton spin density (ρ), T2 relaxation time, magnetization transfer ratio and cross-sectional area were decreased in SCA3, indicating chronic axonopathy. MTR and ρ identified early, subclinical nerve damage in pre-ataxic SCA3 and in SCA3mutation carriers without polyneuropathy and were superior in differentiating between all subgroups. Additionally, microstructural markers correlated well with clinical symptom scores and electrophysiological results. Our data provide a comprehensive characterization of peripheral nerve damage in SCA3 and assist in understanding the mechanisms of the multisystemic disease evolution. Evidence of peripheral nerve involvement prior to the onset of clinically overt ataxia might have important implications for designing early intervention studies.

Non-invasive monitoring of in vitro gastric milk protein digestion kinetics by 1H NMR magnetization transfer

Processing of milk involves heating, which can modify the structure and digestibility of its proteins. In vitro models are useful for studying protein digestion. However, validating these models with in vivo data is challenging. Here, we non-invasively monitor in vitro gastric milk protein digestion by protein-water chemical exchange detected by 1H nuclear magnetic resonance (NMR) magnetization transfer (MT). We obtained either a fitted composite exchange rate (CER) with a relative standard error of ≤10% or the MT ratio (MTR) of the intensity without or with an off-resonance saturation pulse, from just a single spectral acquisition. Both CER and MTR, affected by the variation in the amount of semi-solid protons, decreased during in vitro gastric digestion in agreement with standard protein content analyses. The decrease was slower in heated milk, indicating slower breakdown of the coagulum. Our results open the way to future quantification of protein digestion in vivo by MRI.

Off-resonance saturation as an MRI method to quantify mineral- iron in the post-mortem brain.

PurposeTo employ an off‐resonance saturation method to measure the mineral‐iron pool in the postmortem brain, which is an endogenous contrast agent that can give information on cellular iron status.MethodsAn off‐resonance saturation acquisition protocol was implemented on a 7 Tesla preclinical scanner, and the contrast maps were fitted to an established analytical model. The method was validated by correlation and Bland‐Altman analysis on a ferritin‐containing phantom. Mineral‐iron maps were obtained from postmortem tissue of patients with neurological diseases characterized by brain iron accumulation, that is, Alzheimer disease, Huntington disease, and aceruloplasminemia, and validated with histology. Transverse relaxation rate and magnetic susceptibility values were used for comparison.ResultsIn postmortem tissue, the mineral‐iron contrast colocalizes with histological iron staining in all the cases. Iron concentrations obtained via the off‐resonance saturation method are in agreement with literature.ConclusionsOff‐resonance saturation is an effective way to detect iron in gray matter structures and partially mitigate for the presence of myelin. If a reference region with little iron is available in the tissue, the method can produce quantitative iron maps. This method is applicable in the study of diseases characterized by brain iron accumulation and can complement existing iron‐sensitive parametric methods.

Magnetization transfer ratio: a quantitative imaging biomarker for 5q spinal muscular atrophy.

We quantified peripheral nerve lesions in adults with 5q-linked spinal muscular atrophy (SMA) type 3 by analysing the magnetization transfer ratio (MTR) of the sciatic nerve, and tested its potential as a novel biomarker for macromolecular changes. Eighteen adults with SMA 3 (50% SMA 3a, 50% SMA 3b) and 18 age-/sex-matched healthy controls prospectively underwent magnetization transfer contrast imaging in a 3-Tesla magnetic resonance scanner. Two axial three-dimensional gradient echo sequences, with and without an off-resonance saturation rapid frequency pulse, were performed at the right distal thigh. Sciatic nerve regions of interest were manually traced on 10 consecutive axial slices in the images generated without off-resonance saturation, and then transferred to corresponding slices generated by the sequence with the off-resonance saturation pulse. Subsequently, MTR and cross-sectional areas (CSAs) of the sciatic nerve were analysed. In addition, detailed neurologic, physiotherapeutic and electrophysiologic examinations were conducted in all patients. Sciatic nerve MTR and CSA reliably differentiated between healthy controls and SMA 3, 3a or 3b. MTR was lower in the SMA 3 (P<0.0001), SMA 3a (P<0.0001) and SMA 3b groups (P=0.0020) than in respective controls. In patients with SMA 3, MTR correlated with all clinical scores, and arm nerve compound motor action potentials (CMAPs). CSA was lower in the SMA 3 (P<0.0001), SMA 3a (P<0.0001) and SMA 3b groups (P=0.0006) than in controls, but did not correlate with clinical scores or electrophysiologic results. Magnetization transfer ratio is a novel imaging marker that quantifies macromolecular nerve changes in SMA 3, and positively correlates with clinical scores and CMAPs.

Steady‐state imaging with inhomogeneous magnetization transfer contrast using multiband radiofrequency pulses

PurposeInhomogeneous magnetization transfer (ihMT) is an emerging form of MRI contrast that may offer high specificity for myelinated tissue. Existing ihMT and pulsed MT sequences often use separate radiofrequency pulses for saturation and signal excitation. This study investigates the use of nonselective multiband radiofrequency pulses for simultaneous off‐resonance saturation and on‐resonance excitation specifically for generation of ihMT contrast within rapid steady‐state pulse sequences.Theory and MethodsA matrix‐based signal modeling approach was developed and applied for both balanced steady state free precession and spoiled gradient echo sequences, accounting specifically for multiband pulses. Phantom experiments were performed using a combination of balanced steady state free precession and spoiled gradient echo sequences, and compared with model fits. A human brain imaging exam was performed using balanced steady state free precession sequences to demonstrate the achieved contrast.ResultsA simple signal model derived assuming instantaneous radiofrequency pulses was shown to agree well with full integration of the governing equations and provided fits to phantom data for materials with strong ihMT contrast (PL161 root mean square error = 0.9%, and hair conditioner root mean square error = 2.4%). In vivo ihMT ratio images showed the expected white matter contrast that has been seen by other ihMT investigations, and the observed ihMT ratios corresponded well with predictions.ConclusionsihMT contrast can be generated by integrating multiband radiofrequency pulses directly into both spoiled gradient echo and balanced steady state free precession sequences, and the presented signal modeling approach can be used to understand the acquired signals.

Cross-relaxation parameters in cortical bone assessed with different MR sequences.

This study aimed to show evidence of MR cross-relaxation effects in cortical bone and to compare different MR sequences for the quantification of cross-relaxation parameters. Measurements were performed on bovine diaphysis samples with spectroscopic methods (inversion-recovery, off-resonance saturation) and with a variable flip angle (VFA) UTE imaging method on a 4.7T laboratory-assembled scanner. Cross-relaxation parameter assessment was carried out via a two-pool model simulation with a matrix algebra approach. A proton signal amplitude of 28 Mol/L was observed (equivalent water fraction of 25%). It was attributed to collagen-bound water, with values of ~ 0.3ms, a "long-T2 " proton pool, in exchange with protons from the collagen macromolecules ( of 10-20μs). Magnetization transfer (MT) effects were detected with all sequences. The best precision of model parameters was obtained with off-resonance saturation; the fraction of collagen methylene protons was found in the range of 22-28% and the transverse relaxation time for collagen methylene protons was 11μs (1% precision). The model parameters obtained were compatible with VFA-UTE results but could not be assessed with acceptable accuracy and precision using this method. In vivo MT quantification using off-resonance saturation with a single B1 amplitude and offset frequency may provide information about the relative amount of collagen per unit volume in cortical bone.

Magnetization Transfer Ratio in Peripheral Nerve Tissue: Does It Depend on Age or Location?

Magnetization transfer contrast imaging provides indirect information on the concentration of "bound" water protons and their interactions with "free" water molecules. The purpose of this study is to analyze location- and age-dependent changes in the magnetization transfer ratio (MTR) of lower extremity nerves. Ten younger (20-32 years) and 5 older (50-63 years) healthy volunteers underwent magnetization transfer contrast imaging at 3 Tesla Two 3-dimensional gradient echo sequences with and without an off-resonance saturation pulse (repetition time: 58 milliseconds; echo time: 2.46 milliseconds; band width: 530 Hz/Px; flip angle: α = 7°) were acquired at 3 different locations covering the proximal thigh to the distal lower leg in the group of younger volunteers and at 2 different locations covering the proximal to distal thigh in the group of older volunteers. Sciatic and tibial nerve regions of interest (ROIs) were manually drawn and additional ROIs were placed in predetermined muscles. Magnetization transfer ratios were extracted from respective ROIs and calculated for each individual and location. In young volunteers, mean values of nerve and muscle MTR were not different between the proximal thigh (nerve: 20.34 ± 0.91; muscle: 31.71 ± 0.29), distal thigh (nerve: 19.90 ± 0.98; P = 0.76; muscle: 31.53 ± 0.69; P = 0.87), and lower leg (nerve: 20.82 ± 1.07; P = 0.73; muscle: 32.44 ± 1.11; P = 0.51). An age-dependent decrease of sciatic nerve MTR was observed in the group of older volunteers (16.95 ± 1.2) compared with the group of younger volunteers (20.12 ± 0.65; P = 0.019). Differences in muscle MTR were not significant between older (31.01 ± 0.49) and younger (31.62 ± 0.37; P = 0.20) volunteers. The MTR of lower extremity nerves shows no proximal-to-distal gradient in young healthy volunteers but decreases with age. For future studies using MTR in peripheral nerve disorders, these findings suggest that referencing magnetization transfer contrast values in terms of age, but not anatomical nerve location is required.

MRI gradient-echo phase contrast of the brain at ultra-short TE with off-resonance saturation

Larmor-frequency shift or image phase measured by gradient-echo sequences has provided a new source of MRI contrast. This contrast is being used to study both the structure and function of the brain. So far, phase images of the brain have been largely obtained at long echo times as maximum phase signal-to-noise ratio (SNR) is achieved at TE = T2* (∼40 ms at 3T). The structures of the brain, however, are compartmentalized and complex with a wide range of signal relaxation times. At such long TE, the short-T2 components are largely attenuated and contribute minimally to phase contrast. The purpose of this study was to determine whether proton gradient-echo images of the brain exhibit phase contrast at ultra-short TE (UTE). Our data showed that UTE images acquired at 7 T without off-resonance saturation do not contain significant phase contrast between gray and white matter. However, UTE images of the brain can attain strong phase contrast even at a nominal TE of 106 μs by using off-resonance RF saturation pulses, which provide direct saturation of ultra-short-T2 components and indirect saturation of longer-T2 components via magnetization transfer. In addition, phase contrast between gray and white matter acquired at UTE with off-resonance saturation is reversed compared to that of the long-T2 signals acquired at long TEs. This finding opens up a potential new way to manipulate image phase contrast of the brain. By accessing short and ultra-short-T2 species, MRI phase images may further improve the characterization of tissue microstructure in the brain.

Theoretical analysis and optimization of ultrashort echo time (UTE) imaging contrast with off-resonance saturation

PurposeOff-resonance saturation (ORS) is a tool which can be used in ultrashort echo time (UTE) magnetic resonance imaging to selectively reduce short T2 signals. When these ORS prepared UTE images are subtracted from a non-suppressed UTE acquisition, the short T2 signals are highlighted. The aim of this paper is to develop a theoretical ORS model and optimize short T2 contrast. TheoryUsing a theoretical model the sequence parameters such as saturation flip angle and off-resonance frequency were optimized to maximize short T2 contrast. Bloch simulations were performed to demonstrate the accuracy of the theoretical model. MethodsVolunteer imaging was performed on the knee using different saturation flip angles and off-resonance frequencies using a Fermi RF pulse with a 3D UTE Cones acquisition. ResultsThe off-resonance saturation method showed good long T2 suppression, and highlighted short T2 signals such as the patella tendon. The theoretical signal curves generally agreed with simulated and experimentally measured signals. ConclusionOff-resonance saturation 3D UTE imaging can be used to effectively suppress long T2 signals and highlight short T2 signals. Theoretical modeling can be used to optimize sequence parameters to maximize long T2 suppression and short T2 contrast. Experimental results confirmed the theoretical predictions.

PRO-QUEST: a rapid assessment method based on progressive saturation for quantifying exchange rates using saturation times in CEST.

To develop a new MRI technique to rapidly measure exchange rates in CEST MRI. A novel pulse sequence for measuring chemical exchange rates through a progressive saturation recovery process, called PRO-QUEST (progressive saturation for quantifying exchange rates using saturation times), has been developed. Using this method, the water magnetization is sampled under non-steady-state conditions, and off-resonance saturation is interleaved with the acquisition of images obtained through a Look-Locker type of acquisition. A complete theoretical framework has been set up, and simple equations to obtain the exchange rates have been derived. A reduction of scan time from 58 to 16 minutes has been obtained using PRO-QUEST versus the standard QUEST. Maps of both T1 of water and B1 can simply be obtained by repetition of the sequence without off-resonance saturation pulses. Simulations and calculated exchange rates from experimental data using amino acids such as glutamate, glutamine, taurine, and alanine were compared and found to be in good agreement. The PRO-QUEST sequence was also applied on healthy and infarcted rats after 24 hours, and revealed that imaging specificity to ischemic acidification during stroke was substantially increased relative to standard amide proton transfer-weighted imaging. Because of the reduced scan time and insensitivity to nonchemical exchange factors such as direct water saturation, PRO-QUEST can serve as an excellent alternative for researchers and clinicians interested to map pH changes in vivo.

Abstract P4-02-08: Repeatability and reproducibility of quantitative breast MRI in community imaging centers: Preliminary results

Abstract Introduction: The primary purpose of this study is to evaluate the repeatability and reproducibility of quantitative breast MRI across community imaging centers with the ultimate goal of using these techniques to predict breast cancer response early in the course of neoadjuvant therapy (NAT). Dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted MRI (DW-MRI), and magnetization transfer MRI (MT-MRI) performed early in the course of breast NAT has the potential to predict eventual response prior to changes in tumor size. This enables tailoring of treatment plans and the opportunity to substitute ineffective therapies with alternative approaches. We present preliminary results on the reproducibility and repeatability of T1, apparent diffusion coefficient (ADC), and magnetization transfer ratio (MTR) measurements in normal breast fibroglandular tissue (FGT) in the community setting. Experimental Design: MRI was performed at two community imaging centers and one academic research facility using 3T Siemens Skyra scanners equipped with 8- or 16-channel breast coils. To assess repeatability of the imaging techniques, normal subjects (N=10, ages 22-62) were scanned twice, separated by subject repositioning. To assess reproducibility across sites, normal subjects (N=3) were scanned at three imaging centers. To assess quantitative T1 measurements, subjects were scanned using a spoiled gradient echo (SPGE) sequence and variable flip angles (2, 4, 6, …, 20) with TR/TE = 7.9/2.71 ms and corrected for B1inhomogeneity. To assess the ADC, subjects were scanned using an echo-planar monopolar spin echo sequence with the following parameters: TR/TE = 3000/52 ms and b-values = 0, 200, 800 s/mm2. MT-MRI was acquired using two gradient echo sequences with TR/TE = 48.0/6.40 ms, one with the inclusion of a 1500 Hz off-resonance saturation pulse. FGT was segmented using k-means clustering. Women undergoing NAT for breast cancer are being recruited and scanned with DCE-MRI, DW-MRI, and MT-MRI at baseline (prior to beginning therapy) and three early time points during the course of NAT to evaluate early prediction of response to therapy. Results: Reproducibility scans of normal breast FGT yielded an average difference of 8.4% in T1 measurement, 7.0% in ADC measurement, and 12.7% in MTR measurement between sites. Repeatability scans of the same subject's FGT showed an average percent difference of 6.7% in T1 measurement, 4.5% in ADC measurement, and 11.6% in MTR measurement between the two scans. A multi-site trial performing quantitative DCE-MRI, DW-MRI, and MT-MRI in patients undergoing breast NAT in the community setting (N=16 at the time of submission) has been ongoing to predict response to NAT using quantitative MRI. Conclusion: Quantitative DCE-, DW-, and MT-MRI of the breast is both repeatable and reproducible across MRI scanners in community imaging centers. A quantitative breast MRI protocol can be deployed at community imaging centers for breast cancer patients. These results and ongoing work highlight the feasibility of future clinical dissemination of quantitative MRI for predicting early response to NAT, therefore expanding these novel techniques to a widespread patient population. We acknowledge the support of CPRIT RR160005. Citation Format: Sorace AG, Virostko J, Wu C, Jarrett AM, Barnes SL, Luci J, Patt DA, Goodgame B, Avery S, Yankeelov TE. Repeatability and reproducibility of quantitative breast MRI in community imaging centers: Preliminary results [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-02-08.

Magnetization transfer ratio for the assessment of perianal fistula activity in Crohn's disease.

Assessment of perianal fistulas is important to guide management of Crohn's disease (CD). Our objectives were to analyze the feasibility of magnetization transfer (MT) imaging to assess fistulas and to evaluate its contribution in assessing disease activity. During 15 months, all patients referred for perianal fistulas in CD underwent 3T-MRI including diffusion, T2/T1-weighted gadolinium-enhanced sequences and MT sequences (one with an off-resonance saturation pulse of 800 and one with 1200 Hz). We collected Van Assche score, fistula activity signs by analyzing T2, diffusion and contrast enhancement. We calculated MT ratio (MTR) with a ROI in the largest fistula. Twenty-nine patients (mean 34.9 years, range 17-53) were included. Van Assche score was 11.7, range 4-21. In 22 patients, the fistula presented with a bright T2 and diffusion signal with contrast enhancement, and was characterized as active. Mean MTR was respectively 47.2 (range 12-68) and 34.3 (range 11-57) at 800 and 1200 Hz. MTR at 800 Hz was significantly lower in non-active (34, range 12-55) than in active fistulas (51, range 24-68) (p < 0.02). MTR is feasible for the assessment of fistulas in CD and in the future could be used to help identify active and non-active fistulas. • MTR is feasible for the assessment of perianal fistulas in CD. • MT allows quantitative imaging of perianal fistula activity in CD. • MTR could be used to help identify active and non-active fistulas in CD.

Improvement of the Off-Resonance Saturation, an MRI sequence for positive contrast with SPM particles: Theoretical and experimental study

The SuperParaMagnetic particles (SPM particles) are used as contrast agents in MRI and produce negative contrast with conventional T2 or T2∗-weighted sequences. Unfortunately, the SPM particle detection on images acquired with such sequences is sometimes difficult because negative contrast can be created by artifacts such as air bubbles or calcification. To overcome this problem, new sequences as Off-Resonance Saturation (ORS) were developed to produce positive contrast with SPM particles. This work explores a new way to optimize the contrast generated by the ORS sequence by increasing the number of saturation pulses applied before the imaging sequence. This modified sequence is studied with numerical simulations and experiments on agarose gel phantoms. A theoretical model able to predict the contrast for different values of the sequence parameters is also developed. The results show that the contrast increases with the saturation pulses number with an optimal value of three saturation pulses in order to avoid artifacts and limit the Specific Absorption Rate (SAR) effect. The dependence of the contrast on the SPM particle concentration and sequence parameters is comparable to what was observed for the ORS sequence.

Influence of water compartmentation and heterogeneous relaxation on quantitative magnetization transfer imaging in rodent brain tumors.

The goal of this study was to investigate the influence of water compartmentation and heterogeneous relaxation properties on quantitative magnetization transfer (qMT) imaging in tissues, and in particular whether a two-pool model is sufficient to describe qMT data in brain tumors. Computer simulations and in vivo experiments with a series of qMT measurements before and after injection of Gd-DTPA were performed. Both off-resonance pulsed saturation (pulsed) and on-resonance selective inversion recovery (SIR) qMT methods were used, and all data were fit with a two-pool model only. Simulations indicated that a two-pool fitting of four-pool data yielded accurate measures of pool size ratio (PSR) of macromolecular versus free water protons when there were fast transcytolemmal exchange and slow R1 recovery. The fitted in vivo PSR of both pulsed and SIR qMT methods showed no dependence on R1 variations caused by different concentrations of Gd-DTPA during wash-out, whereas the fitted kex (magnetization transfer exchange rate) changed significantly with R1 . A two-pool model provides reproducible estimates of PSR in brain tumors independent of relaxation properties in the presence of relatively fast transcytolemmal exchange, whereas estimates of kex are biased by relaxation variations. In addition, estimates of PSR in brain tumors using the pulsed and SIR qMT methods agree well with one another. Magn Reson Med 76:635-644, 2016. © 2015 Wiley Periodicals, Inc.

MR-based in vivo follow-up study of Achilles tendon volume and hydration state after ankle-loading activity.

The purpose of this study was to evaluate temporal alterations of the Achilles tendon volume and hydration state after cross-country-running. Achilles tendons of six untrained participants were examined on a 3T MR-scanner before running, immediately afterwards, and in the following 24, 48, and 72 h. Using a 3D-UTE sequence, caudal (CA) and cranial (CR) mid-portion tendon areas were examined with off-resonance saturation ratios (OSR) and T2* relaxation times. Tendon volume was measured with a self-written Matlab-based automated contour detection algorithm (AVAT) in submillimeter T2-weighted MR images. A significant influence of running in caudal (P = 0.017) and cranial OSR values (P = 0.001), tendon volume (P = 0.024), and cranial T2* measurements (P = 0.046), but not in caudal T2* values (P = 0.298) were found. In detail, mean individual OSR and tendon volume measurements demonstrated a similar but inverted course in their values after exercise: initially, OSR values increased after running (and tendon volume decreased), while subsequently a decrease of OSR values (with an increase of tendon volume) could be observed. OSR and tendon volume measurements are able to detect a physiological response of tendons to a mechanical stimulus. After a transient decrease of free water in the Achilles tendon, an increase with a maximum free water content 48 h after ankle loading and a tendency toward normalization after 72 h was found.

Interpretation of magnetization transfer from inhomogeneously broadened lines (ihMT) in tissues as a dipolar order effect within motion restricted molecules

Comparison of off-resonance saturation with single and dual frequency irradiation indicates a contribution of inhomogeneously broadened lines to magnetization transfer in tissues. This inhomogeneous magnetization transfer (ihMT) phenomenon can be exploited to produce images that highlight tissues containing myelin, in vivo. Here, a model for ihMT is described that includes dipolar order effects from magnetization associated with motion-restricted macromolecules. In this model, equal irradiation at positive and negative frequency offsets eliminates dipolar order and achieves greater saturation than irradiation at a single offset frequency using the same power. Fitting of mouse and human volunteer brain data at different irradiation powers and offset frequencies was performed to assess the relevance of the model and approximate tissue parameters. A key parameter in determining ihMT signal was found to be the relaxation time T1D associated with the dipolar order reservoir and the fraction f of the semi-solid, bound magnetization that possessed a nonzero T1D. Indeed, better fits of myelinated tissue were achieved when assuming f≠1. From such fits, estimated T1Ds of mice in the white matter, (34±14)ms, were much longer than in muscle, T1D=(1±1)ms and the average f from white matter volunteer data was 2.2 times greater than that in grey matter. The combination of f and longer T1Ds was primarily responsible for the much higher ihMT in myelinated tissues, and provided explanation for the species variation. This dipolar order ihMT model should help guide future research, pulse sequence optimization, and clinical applications.