Magnetization Transfer MRI Research Articles

474 Magnetization-Transfer MRI As a Non-Invasive Method of Assessing Fibrotic Intestinal Strictures in Patients With Crohn's Disease

474 Magnetization-Transfer MRI As a Non-Invasive Method of Assessing Fibrotic Intestinal Strictures in Patients With Crohn's Disease

Magnetisation transfer MR imaging of the kidney: evaluation at 3.0 T in association with renal function

To evaluate the feasibility of using magnetisation transfer (MT) MRI of the kidney at 3.0T to assess renal function. Forty-four patients who underwent abdominal MRI on a 3.0-T system including gradient-echo (GRE) sequences with and without MT pulse were included. In each patient, MT ratio (MTR) of the renal cortex and medulla was measured by using regions of interest (ROIs) placed on the MTR map image. Regression analysis showed good correlation between estimated glomerular filtration rate (eGFR) and MTR of the renal cortex (r = -0.645, P < 0.0001). Among 44 patients, 22 were categorised as the normal renal function group and 22 were classified as the decreased eGFR group. The mean MTR of the renal cortex in patients with decreased eGFR (mean MTR, 30.7 ± 3.2%) was significantly higher (P < 0.0001) than that in patients with normal renal function (mean MTR, 25.3 ± 2.2%), although the mean MTRs of the renal medulla in the two groups were not significantly different. There was good correlation between eGFR and MTR of the renal cortex derived from MT MRI at 3.0T. This technique may have the potential to evaluate the degree of renal function non-invasively in patients with renal impairment. • Magnetisation transfer techniques can provide new information about renal disease. • MTR values of the renal cortex correlate well with estimated glomerular filtration. • Higher MTR of the renal cortex exists in patients with renal dysfunction. • MT MRI at 3.0T may be useful for evaluating renal function.

Anti–Tumor Necrosis Factor α Prevents Bowel Fibrosis Assessed by Messenger RNA, Histology, and Magnetization Transfer MRI in Rats With Crohnʼs Disease

Treatment of Crohn's disease (CD) with anti-tumor necrosis factor α (TNFα) decreases intestinal inflammation, but the effect on fibrosis remains unclear. We hypothesized that treatment with rat-specific anti-TNFα will decrease the development of intestinal fibrosis in a rat model of CD. We further hypothesized that magnetization transfer magnetic resonance imaging (MT-MRI) will be sensitive in detecting these differences in collagen content. Rats were injected in the distal ileum and cecum with peptidoglycan-polysaccharide (PG-PS) or human serum albumin (control) at laparotomy and then received intraperitoneal injections of rat-specific anti-TNFα or vehicle daily for 21 days after laparotomy. Rats underwent MT-MRI abdominal imaging on day 19 or 20. MT ratio was calculated in the cecal wall. Cecal tissue histologic inflammation was scored. Cecal tissue procollagen, cytokine, and growth factor messenger RNAs were measured by quantitative real-time PCR. PG-PS-injected rats treated with anti-TNFα had less histologic inflammation, and cecal tissue expressed lower levels of proinflammatory cytokine messenger RNAs than vehicle-treated PG-PS-injected rats (IL-1β: 5.59 ± 1.53 versus 10.41 ± 1.78, P = 0.02; IL-6: 23.23 ± 9.33 versus 45.89 ± 11.79, P = 0.07). PG-PS-injected rats treated with anti-TNFα developed less intestinal fibrosis than vehicle-treated PG-PS-injected rats by tissue procollagen I (2.87 ± 0.66 versus 9.28 ± 1.11; P = 0.00002), procollagen III (2.25 ± 0.35 versus 7.28 ± 0.76; P = 0.0000009), and MT-MRI (MT ratio: 17.79 ± 1.61 versus 27.95 ± 1.75; P = 0.0001). Insulin-like growth factor I (2.52 ± 0.44 versus 5.14 ± 0.60; P = 0.0007) and transforming growth factor β1 (2.34 ± 0.29 versus 3.45 ± 0.29; P = 0.006) were also decreased in anti-TNFα-treated PG-PS-injected rats. Anti-TNFα prevents the development of bowel wall inflammation and fibrosis in the PG-PS rat model of CD. MT-MRI measurably demonstrates this decrease in intestinal fibrosis.

Current and emerging quantitative magnetic resonance imaging methods for assessing and predicting the response of breast cancer to neoadjuvant therapy

Reliable early assessment of breast cancer response to neoadjuvant therapy (NAT) would provide considerable benefit to patient care and ongoing research efforts, and demand for accurate and noninvasive early-response biomarkers is likely to increase. Response assessment techniques derived from quantitative magnetic resonance imaging (MRI) hold great potential for integration into treatment algorithms and clinical trials. Quantitative MRI techniques already available for assessing breast cancer response to neoadjuvant therapy include lesion size measurement, dynamic contrast-enhanced MRI, diffusion-weighted MRI, and proton magnetic resonance spectroscopy. Emerging yet promising techniques include magnetization transfer MRI, chemical exchange saturation transfer MRI, magnetic resonance elastography, and hyperpolarized MR. Translating and incorporating these techniques into the clinical setting will require close attention to statistical validation methods, standardization and reproducibility of technique, and scanning protocol design.

Myelin mapping in the central nervous system of living mice using contrast-enhanced magnetization transfer MRI

This work compares magnetization transfer (MT) MRI of living mice with contrast-enhanced MT MRI using intraventricular administration of gadopentetate dimeglumine (Gd-DTPA), systemic administration of MnCl2, and both. In MT MRI at 9.4 T, the contrast-to-noise ratio (CNR) between white matter (WM) and gray matter (GM) increased by 85% after Gd-DTPA injection into the lateral ventricle. When applied in conjunction with manganese-enhanced MT MRI (117 μm isotropic resolution, 6 min measuring time), Gd-DTPA boosted the CNR increase from +56% to +117%. Additional T1 measurements at 2.35 T revealed that intraventricular Gd-DTPA shortens the T1 of GM much more than that of WM, which corresponds to estimated extracellular spaces of 26% in GM and only 15% in WM. These results explain the additional MT contrast enhancement by Gd-DTPA and demonstrate that the T1 shortening by intracellular Mn2+ is well complemented by extracellular Gd-DTPA. The data suggest a high myelin and low water content to hinder access of hydrophilic paramagnetic agents, so that the resulting differential accumulation effectively reduces the MT saturation in water-rich tissues and thereby facilitates the mapping of myelin-rich tissues. Finally, a 156% CNR increase between GM and WM for contrast-enhanced MT MRI at 9.4T using both Gd-DTPA and manganese allowed for 60μm isotropic resolution (102 min measuring time), which delineated myelinated fibers and layers even within GM areas such as the thalamus and cerebellar cortex. Improved MT contrasts were also seen in the cervical spinal cord.

Abstract 1326: Magnetization transfer MRI in pancreatic cancer xenograft models

Abstract Tumor desmoplasia is a common hallmark of pancreatic ductal adenocarcinoma (PDAC), the 4th leading cause of cancer-related mortality. Recent studies clearly indicate that desmoplasia actively facilitates disease progression, metastasis, and drug resistance. Precise quantification of tumor fibrosis levels in PDAC may be critically important for patient staging and for the prediction or monitoring of responses to therapy. The current gold-standard for characterizing desmoplasia_histologic analysis of biopsy samples_is invasive and cannot avoid misrepresentation by reason of sampling error. Therefore, new methods to permit noninvasive quantification of fibrosis levels in PDAC would be particularly useful. Magnetization transfer (MT) MRI can be used to non-invasively probe dynamic physical processes involving the exchange of magnetization between sub-populations of free water protons and those water protons bound to tissue macromolecules. MT-MRI studies have demonstrated that MT contrast (MTC) can be highly sensitive to tissue collagen concentration, the primary component of desmoplasia. Thus, we hypothesized that desmoplasia-associated fibrosis levels in PDAC may be directly reflected in MT-MRI magnetization transfer ratio (MTR) measurements. The purpose of this study was to compare non-invasive MTR measurements to invasive histologic assessments of tumor fibrosis-levels in three mouse xenograft models of PDAC. In this study, MT MRI measurements were performed in 3 PDAC mouse xenograft models. For each of 28 PDAC xenografts, MTR were calculated and compared to histologic fibrosis levels from reference standard trichrome staining. MTR was found to be significantly higher in tumors grown using BxPC-3 cell line (39.4 ± 5.1, mean ± SD) compared to the MTR for the tumors grown from Panc-1 (32.4 ± 2.8) and Capan-1 (27.3 ± 2.9) cell lines (P &amp;lt; 0.05 for each comparison). Histologic measurements showed a similar trend with BxPC-3 tumors demonstrating significantly higher fibrosis levels (percentage of fibrotic tissue area, 6.48 ± 2.59) when compared to Panc-1 (3.54 ± 2.18) and Capan-1 (2.07 ± 1.60) tumors. MTR measurements were well correlated to quantitative fibrosis levels (r = 0.69, P = 0.01). Our results indicated that MTR measurements offer the potential to serve as a valuable in vivo biomarker of desmoplasia in PDAC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1326. doi:1538-7445.AM2012-1326

Magnetization transfer and adiabatic R1ρ MRI in the brainstem of Parkinson’s disease

BackgroundIn addition to classic midbrain pathology, Parkinson’s disease (PD) is accompanied by changes in pontine and medullary brainstem structures. These additional abnormalities may underlie non-motor features as well as play a role in motor disability. Methods: Using novel magnetic resonance imaging (MRI) methods based on rotating frame adiabatic R1ρ (i.e., measurements of longitudinal relaxation during adiabatic full passage pulses) and modified magnetization transfer (MT) MRI mapping, we sought to identify brainstem alterations in nine individuals with mild-moderate PD (off medication) and ten age-matched controls at 4 T. Results: We discovered significant differences in MRI parameters between midbrain and medullary brainstem structures in control subjects as compared to PD patients. Conclusions: These findings support the presence of underlying functional/structural brainstem changes in mild-moderate PD.

Magnetization transfer MRI in pancreatic cancer xenograft models

Magnetization transfer magnetic resonance imaging measurements were performed in three pancreatic ductal adenocarcinoma mouse xenograft models. For each of 28 pancreatic ductal adenocarcinoma xenografts, MT ratios (MTRs) were calculated and compared to histologic fibrosis levels from reference standard trichrome staining. MTR was found to be significantly higher in tumors grown using BxPC-3 cell line (39.4±5.1, mean±SD) compared to the MTR for the tumors grown from Panc-1 (32.4±2.8) and Capan-1 (27.3±2.9) cell lines (P<0.05 for each comparison). Histologic measurements showed a similar trend with BxPC-3 tumors demonstrating significantly higher fibrosis levels (percentage of fibrotic tissue area, 6.48±2.59) when compared to Panc-1 (3.54±2.18) and Capan-1 (2.07±1.60) tumors. MTR measurements were well correlated to quantitative fibrosis levels (r=0.69, P=0.01). Results indicated that MTR measurements offer the potential to serve as a valuable in vivo biomarker of desmoplasia in pancreatic ductal adenocarcinoma.

Magnetic Resonance Techniques in Multiple Sclerosis

Magnetic resonance imaging (MRI) is sensitive to focal multiple sclerosis (MS) lesions. For this reason, conventional MRI measures of the burden of disease derived from dual-echo, fluid-attenuated inversion recovery and postcontrast T1-weighted sequences are regularly used to monitor disease course in patients with confirmed MS and have been included in the diagnostic workup of patients in whom MS is suspected. Other quantitative magnetic resonance (MR)-based techniques with a higher pathological specificity (including magnetization transfer-MRI, diffusion tensor-MRI, and proton MR spectroscopy) have been extensively applied to measure disease burden within focal visible lesions and in the normal-appearing white matter and gray matter of MS patients at different stages of the disease. These methods, combined with functional imaging techniques, are progressively improving our understanding of the factors associated with MS evolution. More recently, the application of new imaging modalities capable of measuring pathological processes related to the disease that have been neglected in the past (eg, iron deposition and perfusion abnormalities) and the advent of high- and ultrahigh-field magnets have provided further insight into the pathobiological features of MS. After a brief summary of the main results obtained from the established and emerging MR methods, this review discusses the steps needed before the latter become suitable for widespread use in the MS research community.

Assessment of lesion pathology in a new animal model of MS by multiparametric MRI and DTI

Magnetic resonance imaging (MRI) is the gold standard for the detection of multiple sclerosis (MS) lesions. However, current MRI techniques provide little information about the structural features of a brain lesion with inflammatory cell infiltration, demyelination, gliosis, acute axonal damage and axonal loss. To identify methods for a differentiation of demyelination, inflammation, and axonal damage we developed a novel mouse model combining cuprizone-induced demyelination and experimental autoimmune encephalomyelitis. MS-like brain lesions were assessed by T1-weighted, T2-weighted, and magnetization transfer MRI as well as by diffusion tensor imaging (DTI). T2-weighted MRI differentiated control and diseased mice, while T1-weighted MRI better reflected the extent of inflammation and axonal damage. In DTI, axonal damage and cellular infiltration led to a reduction of the axial diffusivity, whereas primary demyelination after cuprizone treatment was reflected by changes in radial but not axial diffusivity. Importantly, alterations in radial diffusivity were less pronounced in mice with demyelination, inflammation, and acute axonal damage, indicating that radial diffusivity may underestimate demyelination in acute MS lesions. In conclusion, the combined information from different DTI parameters allows for a more precise identification of solely demyelinated lesions versus demyelinated and acutely inflamed lesions. These findings are of relevance for offering individualized, stage-adapted therapies for MS patients.

In vivo Magnetization Transfer MRI Shows Dysmyelination in an Ischemic Mouse Model of Periventricular Leukomalacia

Periventricular leukomalacia, PVL, is the leading cause of cerebral palsy in prematurely born infants, and therefore more effective interventions are required. The objective of this study was to develop an ischemic injury model of PVL in mice and to determine the feasibility of in vivo magnetization transfer (MT) magnetic resonance imaging (MRI) as a potential monitoring tool for the evaluation of disease severity and experimental therapeutics. Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal day 5 (P5); at P60, in vivo T2-weighted (T2w) and MT-MRI were performed and correlated with postmortem histopathology. In vivo T2w MRI showed thinning of the right corpus callosum, but no significant changes in hippocampal and hemispheric volumes. Magnetization transfer MRI revealed significant white matter abnormalities in the bilateral corpus callosum and internal capsule. These quantitative MT-MRI changes correlated highly with postmortem findings of reduced myelin basic protein in bilateral white matter tracts. Ventriculomegaly and persistent astrogliosis were observed on the ligated side, along with evidence of axonopathy and fewer oligodendrocytes in the corpus callosum. We present an ischemia-induced mouse model of PVL, which has pathologic abnormalities resembling autopsy reports in infants with PVL. We further validate in vivo MRI techniques as quantitative monitoring tools that highly correlate with postmortem histopathology.

P77 Improved magnetization transfer MRI of skeletal muscle in myopathy and neuropathy

P77 Improved magnetization transfer MRI of skeletal muscle in myopathy and neuropathy

Demyelination and degeneration in the injured human spinal cord detected with diffusion and magnetization transfer MRI

Characterizing demyelination/degeneration of spinal pathways in traumatic spinal cord injured (SCI) patients is crucial for assessing the prognosis of functional rehabilitation. Novel techniques based on diffusion-weighted (DW) magnetic resonance imaging (MRI) and magnetization transfer (MT) imaging provide sensitive and specific markers of white matter pathology. In this paper we combined for the first time high angular resolution diffusion-weighted imaging (HARDI), MT imaging and atrophy measurements to evaluate the cervical spinal cord of fourteen SCI patients and age-matched controls. We used high in-plane resolution to delineate dorsal and ventrolateral pathways. Significant differences were detected between patients and controls in the normal-appearing white matter for fractional anisotropy (FA, p<0.0001), axial diffusivity (p<0.05), radial diffusivity (p<0.05), generalized fractional anisotropy (GFA, p<0.0001), magnetization transfer ratio (MTR, p<0.0001) and cord area (p<0.05). No significant difference was detected in mean diffusivity (p=0.41), T1-weighted (p=0.76) and T2-weighted (p=0.09) signals. MRI metrics were remarkably well correlated with clinical disability (Pearson's correlations, FA: p<0.01, GFA: p<0.01, radial diffusivity: p=0.01, MTR: p=0.04 and atrophy: p<0.01). Stepwise linear regressions showed that measures of MTR in the dorsal spinal cord predicted the sensory disability whereas measures of MTR in the ventro-lateral spinal cord predicted the motor disability (ASIA score). However, diffusion metrics were not specific to the sensorimotor scores. Due to the specificity of axial and radial diffusivity and MT measurements, results suggest the detection of demyelination and degeneration in SCI patients. Combining HARDI with MT imaging is a promising approach to gain specificity in characterizing spinal cord pathways in traumatic injury.

MRI is a sensitive marker of subtle white matter pathology in hypoperfused mice

White matter (WM) abnormalities, possibly resulting from hypoperfusion, are key features of the aging human brain. It is unclear, however, whether in vivo magnetic resonance imaging (MRI) approaches, such as diffusion tensor and magnetization transfer MRI are sufficiently sensitive to detect subtle alterations to WM integrity in mouse models developed to study the aging brain. We therefore investigated the use of diffusion tensor and magnetization transfer MRI to measure structural changes in 4 WM tracts following 1 month of moderate hypoperfusion, which results in diffuse WM pathology in C57Bl/6J mice. Following MRI, brains were processed for evaluation of white and gray matter pathology. Significant reductions in fractional anisotropy were observed in the corpus callosum (p = 0.001) and internal capsule (p = 0.016), and significant decreases in magnetization transfer ratio were observed in the corpus callosum (p = 0.023), fimbria (p = 0.032), internal capsule (p = 0.046) and optic tract (p = 0.047) following hypoperfusion. Hypoperfused mice demonstrated diffuse axonal and myelin pathology which was essentially absent in control mice. Both fractional anisotropy and magnetization transfer ratio correlate with markers of myelin integrity/degradation and not axonal pathology. The study demonstrates that in vivo MRI is a sensitive measure of diffuse, subtle WM changes in the murine brain.

Magnetization transfer ratio mapping of intervertebral disc degeneration

The magnetization transfer ratio of the lumbar discs was spatially quantified from age-matched subjects and the nucleus pulposus magnetization transfer ratio was correlated with T2-weighted Pfirrmann grades. A moderate and significant linear correlation between magnetization transfer ratio and Pfirrmann grades was observed, suggesting that nucleus pulposus collagen relative density increases with degeneration. High-resolution axial magnetization transfer ratio maps revealed elevated magnetization transfer ratio in the nucleus pulposa of injured and heavily degenerated discs. In the injured disc, significant elevation in nucleus pulposa magnetization transfer ratio was not accompanied by significant decrease in disc height. This observation may suggest a possible increase in absolute collagen content, in addition to increased collagen relative density. In summary, magnetization transfer MRI of the disc may serve as a noninvasive diagnostic tool for disc degeneration, in addition to other MRI techniques specific to proteoglycan content.

Z-spectroscopy with Alternating-Phase Irradiation

Magnetization transfer (MT) MRI and Z-spectroscopy are tools to study both water–macromolecule interactions and pH-sensitive exchange dynamics between water and the protons of mobile chemical groups within these macromolecules. Both rely on saturation of frequencies offset from water and observation of the on-resonance water signal. In this work, an RF saturation method called Z-spectroscopy with Alternating-Phase Irradiation (ZAPI) is introduced. Based on the T 2-selectivity of the irradiation pulse, ZAPI can be used to separate the different contributions to a Z-spectrum, as well as to study the T 2 distribution of the macromolecules contributing to the MT signal. ZAPI can be run at resonance for water and with low power, thus minimizing problems with specific absorption rate (SAR) limits in clinical applications. In this paper, physical and practical aspects of ZAPI are discussed and the sequence is applied in vitro to sample systems and in vivo to rat head to demonstrate the method.

Thalamic Damage and Long-term Progression of Disability in Multiple Sclerosis

To estimate the relative contributions of baseline thalamic atrophy and abnormalities shown at magnetization transfer (MT) magnetic resonance (MR) imaging, as well as their 12-month changes, in predicting accumulation of disability in a relatively large sample of patients with relapse-onset multiple sclerosis (MS) during an 8-year period. The study was conducted with approval of the institutional review board. Written informed consent was obtained from each participant. Conventional and MT MR imaging of the brain was performed at baseline and at 12-month follow-up in 13 healthy control subjects and 73 patients with relapse-onset MS; participants were monitored with clinical visits for 8 years. The following parameters were evaluated at baseline and at 12-month follow-up: volume of lesions with high signal intensity at T2-weighted imaging, volume of lesions with low signal intensity at T1-weighted imaging, mean lesion MT ratio, thalamic fraction, and thalamic MT ratio. A multivariate analysis was used to evaluate the predictors of long-term neurologic deterioration. At 8-year follow-up, 44 patients showed worsening disability. During follow-up, reduction in thalamic fraction was more pronounced in patients with relapsing-remitting MS than in those with secondary progressive MS (P = .001); thalamic MT ratio decreased only in patients with secondary progressive MS (P = .007). In the multivariable model, baseline thalamic fraction (odds ratio = 0.62, P = .01) and mean percentage change in lesion MT ratio after 12 months (odds ratio = 0.90, P = .04) were independent predictors of worsening disability at 8 years. At baseline, thalamic fraction was correlated with lesion volumes at T2-weighted imaging (r = -0.75, P < .001) and T1-weighted imaging (r = -0.60, P < .001). Thalamic atrophy is correlated with long-term accumulation of disability in patients with MS. White matter lesions are likely to contribute to the loss of tissue seen in the thalamus of patients with MS.

M1230 Magnetization Transfer MRI for In Vivo Imaging Bowel Fibrosis in Patients With Crohn's Disease

M1230 Magnetization Transfer MRI for In Vivo Imaging Bowel Fibrosis in Patients With Crohn's Disease

Imaging biomarkers in multiple sclerosis

Recent years have witnessed impressive advances in the use of magnetic resonance imaging (MRI) for the assessment of patients with multiple sclerosis (MS). Complementary to the clinical evaluation, conventional MRI provides crucial pieces of information for the diagnosis of MS. However, the correlation between the burden of lesions observed on conventional MRI scans and the clinical manifestations of the disease remains weak. The discrepancy between clinical and conventional MRI findings in MS is explained, at least partially, by the limited ability of conventional MRI to characterize and quantify the heterogeneous features of MS pathology. Other quantitative MR-based techniques, however, have the potential to overcome such a limitation of conventional MRI. Indeed, magnetization transfer MRI, diffusion tensor MRI, proton MR spectroscopy, and functional MRI are contributing to elucidate the mechanisms that underlie injury, repair, and functional adaptation in patients with MS. Such techniques are likely to benefit from the use of high-field MR systems and thus allow in the near future providing additional insight into all these aspects of the disease. This review summarizes how MRI is dramatically changing our understanding of the factors associated with the accumulation of irreversible disability in MS and highlights the reasons why they should be used more extensively in studies of disease evolution and clinical trials.

The role of magnetic resonance imaging and spectroscopy in hepatic encephalopathy

Hepatic encephalopathy (HE) is a diverse manifestation of acute and chronic liver failure, ranging from cognitive impairment, only detectable on psychometric evaluation through to confusion, coma and death from cerebral oedema. While there is widespread acceptance of its importance, there is little consensus on how best to diagnose and monitor HE. Clinical descriptions, psychometric testing, electroencephalography and magnetic resonance (MR) imaging (and lately, MR spectroscopy) have all been proposed. MR techniques, in contrast to other modalities, have the benefit of objectivity and of being able to interrogate the brain directly with respect to changes in brain size, function and the metabolic disturbances thought to underlie HE, particularly in the context of astrocyte swelling. Modern clinical MRI scanners with multinuclear MR spectroscopy capabilities and brain mapping software can demonstrate structural and functional cellular changes using volumetric MRI, magnetization transfer MRI, diffusion-weighting MRI, functional MRI with oxygenation measurements and in vivo and in vitro (1)H and (31)P MR spectroscopy. This review describes the relative merits of these techniques and provides guidance on the directions for future research and translation into clinical practice.