Magnetization Transfer Contrast Imaging Research Articles

Fast and motion-robust saturation transfer MRI with inherent B0 correction using rosette trajectories and compressed sensing.

To implement rosette readout trajectories with compressed sensing reconstruction for fast and motion-robust CEST and magnetization transfer contrast imaging with inherent correction of B0 inhomogeneity. A pulse sequence was developed for fast saturation transfer imaging using a stack of rosette trajectories with a higher sampling density near the k-space center. Each rosette lobe was segmented into two halves to generate dual-echo images. B0 inhomogeneities were estimated using the phase difference between the images and corrected subsequently. The rosette-based imaging was evaluated in comparison to a fully sampled Cartesian trajectory and demonstrated on CEST phantoms (creatine solutions and egg white) and healthy volunteers at 3 T. Compared with the conventional Cartesian acquisition, compressed sensing reconstructed rosette images provided image quality with overall higher contrast-to-noise ratio and significantly faster readout time. Accurate B0 map estimation was achieved from the rosette acquisition with a negligible bias of 0.01 Hz between the rosette and dual-echo Cartesian gradient echo B0 maps, using the latter as ground truth. The water-saturation spectra (Z-spectra) and amide proton transfer weighted signals obtained from the rosette-based sequence were well preserved compared with the fully sampled data, both in the phantom and human studies. Fast, motion-robust, and inherent B0-corrected CEST and magnetization transfer contrast imaging using rosette trajectories could improve subject comfort and compliance, contrast-to-noise ratio, and provide inherent B0 homogeneity information. This work is expected to significantly accelerate the translation of CEST-MRI into a robust, clinically viable approach.

PENCIL imaging: A novel approach for neuromelanin sensitive MRI in Parkinson's disease

BackgroundParkinson's disease (PD) is associated with the loss of neuromelanin (NM) and increased iron in the substantia nigra (SN). Magnetization transfer contrast (MTC) is widely used for NM visualization but has limitations in brain coverage and scan time. This study aimed to develop a new approach called Proton-density Enhanced Neuromelanin Contrast in Low flip angle gradient echo (PENCIL) imaging to visualize NM in the SN. MethodsThis study included 30 PD subjects and 50 healthy controls (HCs) scanned at 3T. PENCIL and MTC images were acquired. NM volume in the SN pars compacta (SNpc), normalized image contrast (Cnorm), and contrast-to-noise ratio (CNR) were calculated. The change of NM volume in the SNpc with age was analyzed using the HC data. A group analysis compared differences between PD subjects and HCs. Receiver operating characteristic (ROC) analysis and area under the curve (AUC) calculations were used to evaluate the diagnostic performance of NM volume and CNR in the SNpc. ResultsPENCIL provided similar visualization and structural information of NM compared to MTC. In HCs, PENCIL showed higher NM volume in the SNpc than MTC, but this difference was not observed in PD subjects. PENCIL had higher CNR, while MTC had higher Cnorm. Both methods revealed a similar pattern of NM volume in SNpc changes with age. There were no significant differences in AUCs between NM volume in SNpc measured by PENCIL and MTC. Both methods exhibited comparable diagnostic performance in this regard. ConclusionsPENCIL imaging provided improved CNR compared to MTC and showed similar diagnostic performance for differentiating PD subjects from HCs. The major advantage is PENCIL has rapid whole-brain coverage and, when using STAGE imaging, offers a one-stop quantitative assessment of tissue properties.

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.

Magnetization Transfer Contrast - Is it Sensitive Enough to Differentiate Demyelination from Axonal Loss?

Magnetization transfer contrast imaging (MTC) exploits the principle of exchange of energy between the bound and free protons and was shown to be pathologically informative. There is, however, controversy as to whether it correlates with axonal loss (AL), demyelination (DM), or both. This study addresses the pathophysiological process that underlies the white matter injury using the metric derivative of MTC, magnetization transfer ratio (MTR), and defines the role of MTR in identifying the different stages of inflammation, that is, edema, DM, and AL, using optic nerve as the model. One hundred and forty-two patients with a single, unilateral episode of optic neuritis (ON) were included in the study. Patients were divided into three groups - those with AL, those with DM, and those who were clinically optic neurites but without any electrophysiological changes suggestive of either AL or DM. MTR and electrophysiological studies were performed in the post-acute stage of ON and the results were compared to those obtained from the unaffected optic nerve. MTR was significantly reduced in the optic nerves of both DM and AL groups when compared to that in normal optic nerves (P < 0.001). The difference in MTR between the AL and DM groups did not reach statistical significance. Patient group with acute ON did not show any change in the MTR values compared to the normal controls. MTR is a sensitive technique to identify neuronal injury, whether it is DM or AL. It, however, cannot differentiate these two pathological processes. MTR is not sensitive to identify acute ON.

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.

Magnetic Resonance Neurography: Improved Diagnosis of Peripheral Neuropathies

Peripheral neuropathies account for the most frequent disorders seen by neurologists, and causes are manifold. The traditional diagnostic gold-standard consists of clinical neurologic examinations supplemented by nerve conduction studies. Due to well-known limitations of standard diagnostics and atypical clinical presentations, establishing the correct diagnosis can be challenging but is critical for appropriate therapies. Magnetic resonance neurography (MRN) is a relatively novel technique that was developed for the high-resolution imaging of the peripheral nervous system. In focal neuropathies, whether traumatic or due to nerve entrapment, MRN has improved the diagnostic accuracy by directly visualizing underlying nerve lesions and providing information on the exact lesion localization, extension, and spatial distribution, thereby assisting surgical planning. Notably, the differentiation between distally located, complete cross-sectional nerve lesions, and more proximally located lesions involving only certain fascicles within a nerve can hold difficulties that MRN can overcome, when basic technical requirements to achieve sufficient spatial resolution are implemented. Typical MRN-specific pitfalls are essential to understand in order to prevent overdiagnosing neuropathies. Heavily T2-weighted sequences with fat saturation are the most established sequences for MRN. Newer techniques, such as T2-relaxometry, magnetization transfer contrast imaging, and diffusion tensor imaging, allow the quantification of nerve lesions and have become increasingly important, especially when evaluating diffuse, non-focal neuropathies. Innovative studies in hereditary, metabolic or inflammatory polyneuropathies, and motor neuron diseases have contributed to a better understanding of the underlying pathomechanism. New imaging biomarkers might be used for an earlier diagnosis and monitoring of structural nerve injury under causative treatments in the future.

Predicting cancer malignancy and proliferation in glioma patients: intra-subject inter-metabolite correlation analyses using MRI and MRSI contrast scans.

The non-invasive characterization of glioma metabolites would greatly assist the management of glioma patients in the clinical setting. This study investigated the applicability of intra-subject inter-metabolite correlation analyses for differentiating glioma malignancy and proliferation. A total of 17 negative controls (NCs), 39 low-grade gliomas (LGGs) patients, and 25 high-grade gliomas (HGGs) subjects were included in this retrospective study. Amide proton transfer (APT) and magnetization transfer contrast (MTC) imaging contrasts, as well as total choline/total creatine (tCho/tCr) and total N-acetylaspartate/total creatine (tNAA/tCr) ratios quantified from magnetic resonance spectroscopic imaging (MRSI) were co-registered voxel-wise and used to produce three intra-subject inter-metabolite correlation coefficients (IMCCs), namely, RAPT vs . MTC, RAPT vs . tCho/tCr, and RMTC vs . tNAA/tCr. The correlation between the IMCCs and tumor grade and Ki-67 labeling index (LI) for tumor proliferation were explored. The differences in the IMCCs between the three groups were compared with one-way analysis of variance (ANOVA). Finally, regression analysis was used to build a combined model with multiple IMCCs to improve the diagnostic performance for tumor grades based on receiver operator characteristic curves. Compared with the NCs, gliomas showed stronger inter-metabolic correlations. RAPT vs . MTC was significantly different among the three groups (NC vs. LGGs vs. HGGs: -0.18±0.38 vs. -0.40±0.34 vs. -0.70±0.29, P<0.0001). No significant differences were detected in RMTC vs . tNAA/tCr among the three groups. RAPT vs . MTC and RAPT vs . tCho/tCr correlated significantly with tumor grade (R=-0.41, P=0.001 and R=0.448, P<0.001, respectively). However, only RAPT vs . MTC was mildly correlated with Ki-67 (R=-0.33, P=0.02). RAPT vs . MTC and RAPT vs . tCho/tCr achieved areas under the curve (AUCs) of 0.754 and 0.71, respectively, for differentiating NCs from gliomas; and 0.77 and 0.78, respectively, for differentiating LGGs from HGGs. The combined multi-IMCCs model improved the correlation with the Ki-67 LI (R=0.46, P=0.0008) and the tumor-grade stratification with AUC increased to 0.85 (sensitivity: 80.0%, specificity: 79.5%). This study demonstrated that glioma patients showed stronger inter-metabolite correlations than control subjects, and the IMCCs were significantly correlated with glioma grade and proliferation. The multi-IMCCs combined model further improved the performance of clinical diagnosis.

Unsupervised learning for magnetization transfer contrast MR fingerprinting: Application to CEST and nuclear Overhauser enhancement imaging.

To develop a fast, quantitative 3D magnetization transfer contrast (MTC) framework based on an unsupervised learning scheme, which will provide baseline reference signals for CEST and nuclear Overhauser enhancement imaging. Pseudo-randomized RF saturation parameters and relaxation delay times were applied in an MR fingerprinting framework to generate transient-state signal evolutions for different MTC parameters. Prospectively compressed sensing-accelerated (four-fold) MR fingerprinting images were acquired from 6 healthy volunteers at 3 T. A convolutional neural network framework in an unsupervised fashion was designed to solve an inverse problem of a two-pool MTC Bloch equation, and was compared with a conventional Bloch equation-based fitting approach. The MTC images synthesized by the convolutional neural network architecture were used for amide proton transfer and nuclear Overhauser enhancement imaging as a reference baseline image. The fully unsupervised learning scheme incorporated with the two-pool exchange model learned a set of unique features that can describe the MTC-MR fingerprinting input, and allowed only small amounts of unlabeled data for training. The MTC parameter values estimated by the unsupervised learning method were in excellent agreement with values estimated by the conventional Bloch fitting approach, but dramatically reduced computation time by ~1000-fold. Given the considerable time efficiency compared to conventional Bloch fitting, unsupervised learning-based MTC-MR fingerprinting could be a powerful tool for quantitative MTC and CEST/nuclear Overhauser enhancement imaging.

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.

A deep learning approach for magnetization transfer contrast MR fingerprinting and chemical exchange saturation transfer imaging

Semisolid magnetization transfer contrast (MTC) and chemical exchange saturation transfer (CEST) MRI based on MT phenomenon have shown potential to evaluate brain development, neurological, psychiatric, and neurodegenerative diseases. However, a qualitative MT ratio (MTR) metric commonly used in conventional MTC imaging is limited in the assessment of quantitative semisolid macromolecular proton exchange rates and concentrations. In addition, CEST signals measured by MTR asymmetry analysis are unavoidably contaminated by upfield nuclear Overhauser enhancement (NOE) signals of mobile and semisolid macromolecules. To address these issues, we developed an MTC-MR fingerprinting (MTC-MRF) technique to quantify tissue parameters, which further allows an estimation of accurate MTC signals at a certain CEST frequency offset. A pseudorandomized RF saturation scheme was used to generate unique MTC signal evolutions for different tissues and a supervised deep neural network was designed to extract tissue properties from measured MTC-MRF signals. Through detailed Bloch equation-based digital phantom and in vivo studies, we demonstrated that the MTC-MRF can quantify MTC characteristics with high accuracy and computational efficiency, compared to a conventional Bloch equation fitting approach, and provide baseline reference signals for CEST and NOE imaging. For validation, MTC-MRF images were synthesized using the tissue parameters estimated from the deep-learning method and compared with experimentally acquired MTC-MRF images as the reference standard. The proposed MTC-MRF framework can provide quantitative 3D MTC, CEST, and NOE imaging of the human brain within a clinically acceptable scan time.

Role of the Extracellular Matrix in Loss of Muscle Force With Age and Unloading Using Magnetic Resonance Imaging, Biochemical Analysis, and Computational Models.

The focus of this review is the application of advanced MRI to study the effect of aging and disuse related remodeling of the extracellular matrix (ECM) on force transmission in the human musculoskeletal system. Structural MRI includes (i) ultra-low echo times (UTE) maps to visualize and quantify the connective tissue, (ii) diffusion tensor imaging (DTI) modeling to estimate changes in muscle and ECM microstructure, and (iii) magnetization transfer contrast imaging to quantify the macromolecular fraction in muscle. Functional MRI includes dynamic acquisitions during contraction cycles enabling computation of the strain tensor to monitor muscle deformation. Further, shear strain extracted from the strain tensor may be a potential surrogate marker of lateral transmission of force. Biochemical and histological analysis of muscle biopsy samples can provide “gold-standard” validation of some of the MR findings. The review summarizes biochemical studies of ECM adaptations with age and with disuse. A brief summary of animal models is included as they provide experimental confirmation of longitudinal and lateral force transmission pathways. Computational muscle models enable exploration of force generation and force pathways and elucidate the link between structural adaptations and functional consequences. MR image findings integrated in a computational model can explain and predict subject specific functional changes to structural adaptations. Future work includes development and validation of MRI biomarkers using biochemical analysis of muscle tissue as a reference standard and potential translation of the imaging markers to the clinic to noninvasively monitor musculoskeletal disease conditions and changes consequent to rehabilitative interventions.

Optimizing neuromelanin contrast in the substantia nigra and locus coeruleus using a magnetization transfer contrast prepared 3D gradient recalled echo sequence

Neuromelanin (NM) loss in the substantia nigra (SN) and locus coeruleus (LC) is being investigated as an imaging biomarker for Parkinson’s disease (PD) using magnetization transfer contrast (MTC) magnetic resonance imaging. The MTC pulse operates in a way to suppress tissue with high macromolecular content thereby highlighting the presence of NM in the LC and the SN. The MTC pulse also leads to a reduction in the effective T1 of the tissue. In the past, a 3D gradient echo (GRE) sequence has usually been run with a single flip angle (FA) generally to highlight the T1 shortening effect when trying to visualize NM. We contend that the NM will be best seen with a low FA (relative to the Ernst angle) because the NM has high water content relative to the surrounding tissues. Therefore, the goal of this paper was to optimize the NM contrast in the SN and LC as a function of flip angle using a 3D GRE MTC strategically acquired gradient echo (STAGE) imaging approach. In order to accomplish this, short repeat time (62 ​ms), 3D GRE imaging data were collected for 7 different flip angles ranging from 5° to 40° for 14 healthy volunteers (age range 24–43 years, mean ​± ​SD ​= ​34.8 ​± ​6.0 years, 6 males). By measuring the contrast-to-noise ratio between these structures and the surrounding tissues, we found that the FA showing the best NM contrast was 15° - 20° for the SN and 20° - 25° for the LC. Using STAGE imaging with just two flip angles (15° and 30°) made it possible to quantify not only tissue properties such as T1 and proton density but also to generate synthetic MTC images at an arbitrary FA. These synthetic images make it possible to optimize the contrast for any changes in tissue property that might occur in the LC or SN as a function of age or disease. In conclusion, practically, two scans could be collected in roughly 7 ​min each for both FAs in a standard clinical imaging setting to evaluate the signal intensity and volume of the NM in the LC and SN.

Magnetization transfer ratio quantifies polyneuropathy in hereditary transthyretin amyloidosis.

ObjectiveTo quantify peripheral nerve lesions in symptomatic and asymptomatic hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PNP) by analyzing the magnetization transfer ratio (MTR) of the sciatic nerve, and to test its potential as a novel biomarker for macromolecular changes.MethodsTwenty‐five patients with symptomatic ATTRv‐PNP, 30 asymptomatic carriers of the mutant transthyretin gene (mutTTR), and 20 age‐/sex‐matched healthy controls prospectively underwent magnetization transfer contrast imaging at 3 Tesla. Two axial three‐dimensional gradient echo sequences with and without an off‐resonance saturation rapid frequency pulse were conducted at the right distal thigh. Sciatic nerve regions of interest were manually drawn on 10 consecutive axial slices in the images without off‐resonance saturation, and then transferred to the corresponding slices that were generated by the sequence with the off‐resonance saturation pulse. Subsequently, the MTR and cross‐sectional area (CSA) of the sciatic nerve were evaluated. Detailed neurologic and electrophysiologic examinations were conducted in all ATTRv‐PNP patients and mutTTR‐carriers.ResultsSciatic nerve MTR and CSA reliably differentiated between ATTRv‐PNP, mutTTR‐carriers, and controls. MTR was lower in ATTRv‐PNP (26.4 ± 0.7; P < 0.0001) and in mutTTR‐carriers (32.6 ± 0.8; P = 0.0005) versus controls (39.4 ± 2.1), and was also lower in ATTRv‐PNP versus mutTTR‐carriers (P = 0.0009). MTR correlated negatively with the NIS‐LL and positively with CMAPs and SNAPs. CSA was higher in ATTRv‐PNP (34.3 ± 1.7 mm3) versus mutTTR‐carriers (26.0 ± 1.1 mm3; P = 0.0005) and versus controls (20.4 ± 1.2 mm3; P < 0.0001). CSA was also higher in mutTTR‐carriers versus controls.InterpretationMTR is a novel imaging marker that can quantify macromolecular changes in ATTRv‐PNP and differentiate between symptomatic ATTRv‐PNP and asymptomatic mutTTR‐carriers and correlates with electrophysiology.

Fractal Analysis of Cardiac Fibrosis Patterns Derived From Magnetization Transfer Contrast MRI in Patients With End-Stage Renal Disease.

OBJECTIVE. The purpose of this study is to use fractal analysis to characterize diffusely fibrotic, focally fibrotic, and healthy myocardium in patients with end-stage renal disease (ESRD) on the basis of previously published magnetization transfer (MT) contrast images. MATERIALS AND METHODS. The MT ratio values of patients with ESRD (n = 34) and healthy control subjects (n = 19) were used to construct anatomically faithful 3D left ventricular reconstructions. Established MT ratio threshold values were used to define healthy, diffusely enhanced, focally enhanced, and total enhanced tissue domains. The fractal dimension (FD) for reach domain was calculated using a 3D box-counting algorithm. RESULTS. Patients with ESRD showed a higher FD across all fibrotic domains compared with control subjects, in whom diffusely and focally enhanced myocardium showed largely planar distributions (mean [± SD] FD, 2.12 ± 0.02 and 1.92 ± 0.09, respectively), whereas the combined domain was fractal in 3D (mean FD, 2.41 ± 0.04). The FD and volume of fibrotic tissue were logarithmically correlated in the population with ESRD. Fractal analysis of MT-weighted cardiac MRI data revealed that the geometric characteristics of cardiac scar in patients with ESRD transition from fractal in 2D to planar in 2D to fractal in 3D as scar volume increases. CONCLUSION. Fatal arrhythmias in individuals with ESRD are increasingly attributed to cardiac fibrosis. Histologic analysis reveals that fibrosis progresses via a fractal expansion pattern. The method presented in this study can be applied to characterize the irregular space-filling morphometry of any pathologic substrate identified by contrast enhancement across noninvasive imaging modalities.

Improving acute demyelinating lesion detection: which T1-weighted magnetic resonance acquisition is more sensitive to gadolinium enhancement?

Because of the need for a standardized and accurate method for detecting multiple sclerosis (MS) inflammatory activity, different magnetic resonance (MR) acquisitions should be compared in order to choose the most sensitive sequence for clinical routine. To compare the sensitivity of a T1-weighted image to a single dose of gadolinium (Gd) administration both with and without magnetization transfer to detect contrast enhancement in active demyelinating focal lesions. A sample of relapsing-remitting MS patients were prospectively examined separately by two neuroradiologists using a 1.5 Tesla scanner. The outcome parameters were focused on Gd-enhancement detection attributed to acute demyelination. All MR examinations with at least one Gd-enhancing lesion were considered positive (MR+) and each lesion was analyzed according to its size and contrast ratio. Thirty-six MR examinations were analyzed with a high inter-observer agreement for MR+ detection (k coefficient > 0.8), which was excellent for the number of Gd-enhancing lesions (0.91 T1 spin-echo (SE), 0.88 T1 magnetization transfer contrast (MTC) sequence and 0.99 magnetization-prepared rapid acquisition with gradient-echo (MPRAGE). Significantly more MR+ were reported on the T1 MTC scans, followed by the T1 SE, and MPRAGE scans. Confidently, the T1 MTC sequence demonstrated higher accuracy in the detection of Gd-enhancing lesions, followed by the T1 SE and MPRAGE sequences. Further comparisons showed that there was a statistically significant increase in the contrast ratio and area of Gd-enhancement on the T1 MTC images when compared with both the SE and MPRAGE images. Single-dose Gd T1 MTC sequence was confirmed to be the most sensitive acquisition for predicting inflammatory active lesions using a 1.5 T magnet in this sample of MS patients.

Determination of Activity of Multiple Sclerosis (MS) Lesions in the Brain by Different Magnetic Resonance Imaging (MRI) Pulse Sequences

AbstractBackground: Multiple sclerosis is one of the commonest causes of chronic neurological disability in young and middle aged people. MRI offers a unique in-vivo investigative tool for its evaluation.Aim of Study: To reveal the value of different MRI pulse sequences in evaluation of multiple sclerosis affection of the brain.Patients and Methods: This is a prospective hospital analytic study enrolling 25 patients diagnosed to have definite multiple sclerosis according to the McDonald's Criteria for diagnosing multiple sclerosis during the period from April 2016 to February 2017. The study was conducted in the MRI Unit of the Radiology Department of Assiut University Hos-pital.Results: All the enhancing lesions showed restricted diffusion in DW images at high b values accounting for 100% sensitivity and negative predictive value of DWI pulse se-quence. On the other hand, some of the non-enhancing MS lesions, showed diffusion restriction in DW images, assuming a positive predictive value and specificity of 36.3% and 94% respectively. Post-contrast Magnetization Transfer Contrast (MTC) images could significantly detect higher number of enhancing MS lesions than standard T1W-SE images. All the enhancing lesions depicted on post-contrast T 1 W-SE sequence were also seen enhancing in MTC images, but more conspic-uous.Conclusion: Diffusion weighted imaging and magnetiza-tion transfer imaging provide suitable investigative tools for determination of multiple sclerosis activity.

Magnetization transfer contrast MRI in GFP‑tagged live bacteria.

Green fluorescent protein (GFP) is a widely utilized molecular reporter of gene expression. However, its use in in vivo imaging has been restricted to transparent tissue mainly due to the tissue penetrance limitation of optical imaging. Magnetization transfer contrast (MTC) is a magnetic resonance imaging (MRI) methodology currently utilized to detect macromolecule changes such as decrease in myelin and increase in collagen content. MTC MRI imaging was performed to detect GFP in both in vitro cells and in an in vivo mouse model to determine if MTC imaging could be used to detect infection from Pseudomonas aeruginosa in murine tissues. It was demonstrated that the approach produces values that are protein specific and concentration dependent. This method provides a valuable, non-invasive imaging tool to study the impact of novel antibacterial therapeutics on bacterial proliferation and perhaps viability within the host system, and could potentially suggest the modulation of bacterial gene expression within the host when exposed to such compounds.

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.

Magnetization transfer contrast imaging detects early white matter changes in the APP/PS1 amyloidosis mouse model.

While no definitive cure for Alzheimer's disease exists yet, currently available treatments would benefit greatly from an earlier diagnosis. It has previously been shown that Magnetization transfer contrast (MTC) imaging is able to detect amyloid β plaques in old APP/PS1 mice. In the current study we investigated if MTC is also able to visualize early amyloid β (Aβ) induced pathological changes. In a cross-sectional study, a comparison was made between the MT ratio of wild type (WT) and APP/PS1 mice at 2, 4, 6, 8 and 24 months of age. We observed an increased MT-ratio in the cortex of 24 month old APP/PS1 mice as compared to WT mice. However, when comparing the MT-ratio of the cortex of WT mice with the MT-ratio of the APP/PS1 mice at 2, 4, 6 or 8 months of age, no significant changes could be observed. In contrast to the cortex, we consistently observed a decreased MT-ratio in the splenium of 4, 6 and 8 month old APP/PS1 mice as compared to age-matched WT mice. Lastly, the decreased MT-ratio in the splenium of APP/PS1 mice correlated to the Aβ plaque deposition, astrogliosis and microgliosis. This MT-ratio decrease did however not correlate to the myelin content. Combined, our results suggest that MTC is able to visualize early Aβ-induced changes in the splenium but not the cortex of APP/PS1 mice.•MTC visualizes cortical Aβ-induced changes at very old ages.•MTC visualizes longitudinal Aβ-induced white matter changes in young APP/PS1 mice.•Changes in white matter MT-ratios correlate to Aβ plaque load, astro- and microgliosis.

Simultaneous fat saturation and magnetization transfer contrast imaging with steady-state incoherent sequences.

This work combines an n-dimensional fat sat(uration) radiofrequency (RF) pulse with steady-state incoherent (SSI) pulse sequences, e.g., spoiled gradient-echo sequence, to simultaneously produce B0 insensitive fat suppression and magnetization transfer (MT) contrast. This pulse is then referred to as "fat sat and MT contrast pulse." We discuss the features of the fat sat and MT contrast pulse and the MT sensitivities of the SSI sequences when combining with fat sat. Moreover, we also introduce an adapted RF spoiling scheme for SSI sequences with fat sat. Simulations and phantom experiments were conducted to demonstrate the adapted RF spoiling. Fat suppression and MT effects are shown in 3T phantom experiments and in vivo experiments, including brain imaging, cartilage imaging, and angiography. To ensure that the sequence reaches steady state, the adapted RF spoiling is required for fat sat SSI sequences. Fat sat and MT contrast pulse works robustly with field inhomogeneity and also produces MT contrasts. SSI sequences with fat sat and MT contrast pulse and adapted RF spoiling can robustly produce fat suppressed and MT contrast images in the presence of field inhomogeneity.