Inversion Efficiency Model Yields Improved Accuracy in MP2RAGE‐Based T1 Mapping in the Human Brain at 7.0T

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.

Concurrent saturation transfer contrast in in vivo brain by a uniform magnetization transfer MRI

The remarkable success of magnetic resonance imaging of adult brain relates to the unusually large ratio of the longitudinal relaxation rates 1/T1 of white and gray matter, approximately 2:1 at physiological temperature and traditional imaging fields. Several investigators have conjectured that myelin is the source of the greater 1/T1 of white matter without, however, suggesting details of the molecular mechanisms responsible. From measurements of the magnetic field dependence of 1/T1 (NMRD profiles) of adult and neonatal gray and white matter at 5 and 35 degrees C, we find a thermally activated contribution to the NMRD profile of adult white matter that is not present in the profiles of either adult gray or neonatal gray and white matter. We attribute this contribution to myelin and develop a quantitative model that accounts for the unique relaxation behavior of myelinated white matter. We find that myelin water, 15% of the total, has a relatively short T1 that arises from an unexpectedly large interaction with myelin lipid; when cast in terms of an interaction over the entire myelin bilipid-water interface, it is sevenfold greater than the analogous protein-water interfacial interaction. Its magnitude remains to be accounted for, but cholesterol, known to alter the relaxation rates of lipid protons, may play an important role. The contribution of myelin to 1/T1 at physiological temperatures is attributed to thermally activated transmembrane diffusion of water and, hence, more rapid mixing of axonal and the rapidly relaxing myelin water molecules.

The authors addressed the hypothesis that interactions with creatine kinase (CK) play a role in the off-resonance magnetization transfer (MT) effect of creatine in skeletal muscle. Toward that aim, (1)H MT studies were done on hindleg muscle in wild-type mice and in transgenic mice, lacking cytoplasmic CK and/or mitochondrial CK. The (1)H MT effect was essentially identical in wild-type muscle and the two single CK knock-out muscles, while moderately decreased in tissue lacking both CK isoforms. (31)P-NMR showed no off-resonance (31)P MT effect in skeletal muscle for PCr in any of the mice, while the enzymatic CK reaction flux was circa 0.2-0.3 sec(-1) in the wild-type muscle and in muscle deficient in mitochondrial CK. The CK enzyme flux was negligible in the other two CK knock-outs. These data suggest that CK plays a minor role in the (1)H MT effect of creatine. Irrespective of the underlying mechanism the creatine MT phenomenon probably has no significant consequences for the thermodynamic availability of total creatine to the CK reaction.

Magnetization transfer (MT) contrast is a new technique that may improve contrast in magnetic resonance imaging. High-protein tissues have a greater MT effect, resulting in a decrease in signal intensity. This study evaluates the MT technique on normal and abnormal liver tissue on a low-field system. The magnitude of the magnetization transfer was studied to determine its effect on image visualization and tissue characterization. Ten volunteers and 25 patients with benign and malignant liver pathology, including left lateral segment hepatectomy, were imaged on a 0.1 T system. Gradient-recalled-echo T2-weighted sequence pairs were obtained with and without MT pulse saturation. Signal intensity measurements were made using region-of-interest tracings in liver, spleen, skeletal muscle, fat, and selected liver pathology. Liver-to-lesion contrast ratios and conspicuity changes were analyzed. The average signal intensity decrease for normal liver was .27. Skeletal muscle demonstrated the greatest MT effect (.48), while fat showed minimal (.01) MT change. Two hemangiomas and two liver cysts showed a small MT effect (.13 and .02, respectively). Of the malignant lesions imaged, melanoma metastases showed a mean MT effect of .34, while hepatomas showed mean effect of .15. Edematous liver tissue had an intermediate mean effect of .18. While T2 sequences are more versatile for standard liver imaging, an MT sequence may be helpful for tissue characterization in specific imaging situations. Melanoma metastases and hepatomas demonstrated significant MT effect and increased conspicuity of the malignant lesions.

One of the most remarkable achievements of in vivo NMR spectroscopy has been the detection of rapid enzyme-catalyzed exchange reactions using phosphorus-31 magnetic resonance spectroscopy-based magnetization transfer experiments. In this paper, we report, for the first time, the in vivo carbon magnetization transfer (CMT) effect and in vivo detection of the CMT effects of the alpha-ketoglutarate <--> glutamate and the oxaloacetate <--> aspartate reactions, both of which are catalyzed by aspartate aminotransferase. By saturating the carbonyl carbon of alpha-ketoglutarate at 206 ppm in alpha-chloralose anesthetized adult rat brain, the unidirectional glutamate --> alpha-ketoglutarate flux was determined to be 78 +/- 9 mumol/g/min (mean +/- SD, n = 11) following i.v. infusion of [1,6-(13)C(2)]D-glucose. Contribution from aspartate aminotransferase-catalyzed partial reactions to the observed CMT effects was emphasized. Because of the large chemical shift separation between the alpha-carbons of the amino acids and the carbonyl carbons of the corresponding cognate keto acids, the spillover of the saturation radiofrequency pulses to the alpha-carbon resonances was negligible. The results indicate that the magnetization transfer effects of aspartate aminotransferase-catalyzed reactions can be used as new biomarkers accessible to non-invasive in vivo magnetic resonance spectroscopy techniques.

To compare magnetization transfer (MT) and CEST effects between 1.5T and 3T in phantom and in vivo experiments. A pulsed saturation scheme using block-shaped pulses separated by gaps was used to overcome the single RF amplifier duty cycle limitations of a clinical 1.5T scanner. Modeling was performed by incorporating the extended phase graph formalism into a Bloch-McConnell simulation. Two saturation pulse types (with long and short pulses) were used. Estimated parameters for MT (the semi-solid pool fraction, M0B ; the semi-solid transverse relaxation time, T2B ) and CEST (asymmetry; areas) were compared between 1.5T and 3T in phantoms and in the healthy brain. Improved fits were shown after inclusion of extended phase graphs. Semi-solid pool fractions in phantom (for agar with ammonium chloride) were higher for short compared to long pulses at 3T (by 19% over all concentrations) and higher at 1.5T compared to 3T (by 5%) using short pulses. In the in vivo experiments, differentiation of white and gray matter was seen in the brain at both field strengths with improved white-gray matter contrast at 3T. In white matter, the mean semi-solid fractions were 18 ± 2% at 3T and 15 ± 2% at 1.5T. The CEST asymmetry in white matter was negative (-4.9 ± 0.4%) at 3T and zero (0.0 ± 0.3%) at 1.5T. The pulsed saturation method with short pulses, using the extended phase graph formalism in the Bloch McConnell simulations, led to improved model fits to the data, when compared to those without extended phase graphs.

The signal-to-noise ratio of the perfusion image (SNR(perfu)) in a spin-tagging experiment is shown to depend on both the degree of spin labeling (alpha) and the signal-to-noise ratio of the proton density images (SNRimage) used to calculate the perfusion image. When a single radiofrequency (RF) coil is used for both spin tagging and magnetic resonance (MR) imaging, magnetization transfer (MT) effects decrease SNRimage, and therefore SNRperfu, by an amount that depends on the strength B1 and offset deltaomega (determined by the gradient strength G(I) applied during spin tagging) of the labeling RF pulse. It is shown that by optimizing B1 and G(I), it is possible to reduce MT effects and thus increase SNRimage, while leaving alpha unchanged. As a result, SNRperfu, will be improved. An equation for calculating perfusion under general conditions of such reduced MT effects is derived and shown to give perfusion rates that are independent of the strength and offset of the labeling RF irradiation.

Magnetization transfer and T2 quantitation in normal appearing cortical gray matter and white matter adjacent to focal abnormality in patients with traumatic brain injury.

Background: This study aimed to establish normal regional Magnetization Transfer Ratio (MTR) values in white and grey matter using 3-Tesla MRI in healthy adult subjects, with a particular focus on cortical and deep brain structures. It also aims to assess the variability of these values and provide a baseline for further pathological studies. Materials and Methods: Seventy healthy volunteers (28 females, 42 males, mean age 28 years) were included. MRI scans were performed using a 3.0 Tesla MRI scanner. Conventional cranial MRI sequences were acquired, followed by Magnetization Transfer Imaging (MTI) with off-resonance pulses. MTR maps were generated from proton density-weighted images obtained with and without magnetization transfer pre-pulses. Measurements were performed in 31 white matter and 9 grey matter regions, with additional assessments of CSF for noise control. Statistical analysis was carried out to compare MTR values across different brain regions. Results: The mean MTR value was significantly higher in white matter (23.9 ± 0.21) compared to grey matter (17.3 ± 0.77). The corpus callosum had the highest MTR values within the white matter, particularly in the splenium, while the thalamus exhibited the highest MTR values in the grey matter. Regional variations were observed, with higher MTR values in the occipital and temporal lobes and lower values in the frontal and parietal lobes. MTR measurements showed excellent intra-observer (ICC &amp;gt; 0.9) and good inter-observer reliability (ICC 0.80–0.90). Conclusions: This study provides detailed MTR mapping of normal brain tissue, highlighting significant regional dif-ferences between white and grey matter. The findings offer valuable baseline data for assessing structural changes in CNS diseases and for evaluating the efficacy of therapeutic interventions. MTR measurements demonstrate high reproducibility, making this technique a reliable tool in clinical and research applications for monitoring pathological alterations in the central nervous system.

Motivation: Very little is known about magnetization transfer (MT) effects of the lung and MT contrast might be a biomarker for pulmonary fibrosis and other lung tissue abnormalities. Goal(s): To develop a clinically applicable method for detecting in-vivo MT contrast in the lung. Approach: A self-gated 3D half-radial balanced steady state free precession sequence (bSTAR) in combination with RF pulse prolongation was used to explore MT effects in the lung at 0.55T. Results: In volunteers, average whole lung MTR values of 32.4 ± 3.5 [pu] were observed and showed good reproducibility. Impact: This work shows that high-resolution in-vivo magnetization transfer imaging of the lung is feasible and reproducible at 0.55T in free-breathing and within clinically relevant scan times, offering excellent prospects to detect lung tissue abnormalities such as fibrosis.

Consideration of slice profiles in inversion recovery Look–Locker relaxation parameter mapping

Stereotactic MR-guided Adaptive Radiation Therapy (SMART) dose painting for hypoxia has potential to improve treatment outcomes, but clinical implementation on low-field MR-Linac faces substantial challenges due to dramatically lower signal-to-noise ratio (SNR) characteristics. While quantitative MRI and T1 mapping of hypoxia biomarkers show promise, T1-to-noise ratio (T1NR) optimization at low fields is paramount, particularly for the clinical implementation of oxygen-enhanced (OE)-MRI. The 3D Magnetization Prepared (2) Rapid Gradient Echo (MP2RAGE) sequence stands out for its ability to acquire homogeneous T1-weighted contrast images with simultaneous T1 mapping. To optimize MP2RAGE for low-field T1 mapping; conduct experimental validation in a ground-truth phantom; establish feasibility and reproducibility of low-field MP2RAGE acquisition and T1 mapping in healthy volunteers. The MP2RAGE optimization was performed to maximize the contrast-to-noise ratio (CNR) of T1 values in white matter (WM) and gray matter (GM) brain tissues at 0.35T. Low-field MP2RAGE images were acquired on a 0.35T MR-Linac (ViewRay MRIdian) using a multi-channel head coil. Validation of T1 mapping was performed with a ground-truth Eurospin phantom, containing inserts of known T1 values (400-850ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T1 maps. Mean (±SD) T1 relative error, T1NR, and intersession coefficient of variation (CV) were determined. Whole-brain MP2RAGE scans were acquired in 5 healthy volunteers across two sessions (A and B) and T1 maps were generated. Mean (±SD) T1 values for WM and GM were determined. Whole-brain T1 histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel-by-voxel T1 difference maps were generated to evaluate 3D spatial variation. Low-field MP2RAGE optimization resulted in parameters: MP2RAGETR of 3250ms, inversion times (TI1/TI2) of 500/1200ms, and flip angles (α1/α2) of 7/5°. Eurospin T1 maps exhibited a mean (±SD) relative error of 3.45%±1.30%, T1NR of 20.13±5.31, and CV of 2.22%±0.67% across all inserts. Whole-brain MP2RAGE images showed high anatomical quality with clear tissue differentiation, resulting in mean (±SD) T1 values: 435.36±10.01ms for WM and 623.29±14.64ms for GM across subjects, showing excellent concordance with literature. Whole-brain T1 histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel-level WM and GM T1 values. Reproducibility analysis revealed a CV of 0.46%±0.31% and 0.35%±0.18% for WM and GM, respectively. Voxel-by-voxel T1 difference maps show a normal 3D spatial distribution of noise in WM and GM. Low-field MP2RAGE proved effective in generating accurate, reliable, and reproducible T1 maps with high T1NR in phantom studies and in vivo feasibility established in healthy volunteers. While current work is focused on refining the MP2RAGE protocol to enable clinically efficient OE-MRI, this study establishes a foundation for TOLD T1 mapping for hypoxia biomarkers. This advancement holds the potential to facilitate a paradigm shift toward MR-guided biological adaptation and dose painting by leveraging 3D hypoxic spatial distributions and improving outcomes in conventionally challenging-to-treat cancers.

In established multiple sclerosis, magnetization transfer ratio (MTR) histograms reveal abnormalities of normal-appearing white matter (NAWM) and grey matter (NAGM). The aim of this study was to investigate for such abnormalities in a large cohort of patients presenting with clinically isolated syndromes suggestive of multiple sclerosis. Magnetization transfer imaging was performed on 100 patients (67 women, 33 men, median age 32 years) a mean of 19 weeks (SD 3.8, range 12-33 weeks) after symptom onset with a clinically isolated syndrome and in 50 healthy controls (34 women, 16 men, median age 32.5 years). SPM99 software was used to generate segmented NAWM and NAGM MTR maps. The volumes of T2 lesions, white matter and grey matter were calculated. Eighty-one patients were followed up clinically and with conventional MRI after 3 years (n = 61) or until they developed multiple sclerosis if this occurred sooner (n = 20). Multiple regression analysis was used to investigate differences between patients and controls with age, gender and volume measures as covariates to control for potential confounding effects. The MTR histograms for both NAWM and NAGM showed a reduction in the mean (NAWM, 38.14 versus 38.33, P = 0.001; NAGM 32.29 versus 32.50, P = 0.009; units in pu) and peak location, with a left shift in the histogram. Mean NAWM and NAGM MTR were also reduced in the patients who developed clinically definite multiple sclerosis and multiple sclerosis according to the McDonald criteria but not in the 24 patients with normal T2-weighted brain magnetic resonance imaging (MRI). MTR abnormalities occur in the NAWM and NAGM at the earliest clinical stages of multiple sclerosis.

ABSTRACTNeuromelanin (NM) magnetic resonance imaging has been used to evaluate the loss of melanized neurons in the substantia nigra, the main characteristic of Parkinson disease, typically by measuring the contrast ratio (CR) between the NM‐rich areas and the cerebral peduncles in the midbrain. Neuromelanin contrast can be generated by employing a 3D gradient‐echo (GRE) sequence with magnetization transfer (MT). In this work, we first evaluated the effect of the MT pulse frequency on the CR and contrast‐to‐noise ratio (CNR), analyzing a large frequency range from 500 to 100K Hz. Secondly, the impact of the 3D GRE sequence flip angle (FA) was evaluated using angles from 5° to 40°. Additionally, images were acquired both with and without MT for each FA, providing an opportunity to examine the effect of MT on tissue proton density, T1, and T2* values. Results showed that the highest CR and CNR were obtained for the lower MT frequencies (500–2000 Hz) and lower FAs (5°–10°). The lower FAs improved the visualization of the neuromelanin‐rich area in the substantia nigra and facilitated delineating its volume. In addition, this work showed that the MT pulse decreased the T1 and PD of the tissue. Furthermore, simulations supported the obtained in vivo results.