WHO/ISUP grade and pathological T stage of clear cell renal cell carcinoma: value of ZOOMit diffusion kurtosis imaging and chemical exchange saturation transfer imaging.

OBJECTIVES: To evaluate the value of ZOOMit diffusion kurtosis imaging (DKI) and chemical exchange saturation transfer (CEST) imaging in predicting WHO/ISUP grade and pathological T stage in clear cell renal cell carcinoma (ccRCC). METHODS: Forty-six patients with ccRCC were included in this retrospective study. All participants underwent MRI including ZOOMit DKI and CEST. The non-Gaussian mean kurtosis (MK), mean diffusivity (MD), magnetization transfer ratio asymmetry (MTRasym (3.5 ppm)), and Ssat (3.5 ppm)/S0 were analyzed based on different WHO/ISUP grades and pT stages. Binary logistic regression was used to identify the best combination of the parameters. Pearson's correlation coefficients were calculated between CEST and diffusion-related parameters. RESULTS: The ADC, MD, and Ssat (3.5 ppm)/S0 values were significantly lower for higher WHO/ISUP grade tumors, whereas the MK and MTRasym (3.5 ppm) were higher in higher WHO/ISUP grade and higher pT stage tumors. MTRasym (3.5 ppm) combined with MD (AUC, 0.930; 95% CI, 0.858-1.000) showed the best diagnostic efficacy in evaluating the WHO/ISUP grade. MTRasym (3.5 ppm) and MK were mildly positively correlated (r = 0.324, p = 0.028). Ssat (3.5 ppm)/S0 was moderately positively correlated with ADC (r = 0.580, p < 0.001), mildly positively correlated with MD (r = 0.412, p = 0.005), and moderately negatively correlated with MK (r = -0.575, p < .001). CONCLUSION: The microstructural and biochemical assessment of ZOOMit DKI and CEST allowed for the characterization of different WHO/ISUP grades and pT stages in ccRCC. MTRasym (3.5 ppm) combined with MD showed the best diagnostic performance for WHO/ISUP grading. KEY POINTS: • Both diffusion kurtosis imaging (DKI) and chemical exchange saturation transfer (CEST) can be used to predict the WHO/ISUP grade and pathological T stage. • MTRasym (3.5 ppm) combined with MD showed the highest AUC (0.930; 95% CI, 0.858-1.000) in WHO/ISUP grading. • MTRasym at 3.5 ppm showed a positive correlation with mean kurtosis.

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

BACKGROUND AND OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Differentiating active from Inactive Sacroiliitis in ankylosing spondylitis by combination of DWI and Magnetization Transfer Imaging.

Objectives: To evaluate lesions of sacroiliac joint (SIJ) by combination of diffusion-weighted imaging (DWI) and magnetization transfer (MT). Methods: A retrospective study was used in this study. Forty-nine ankylosing spondylitis (AS) patients admitted to The China Academy of Chinese Medical Sciences Xiyuan Hospital from May 2020 to October 2020 were collected into active and inactive groups. Twenty-two healthy volunteers were recruited. Apparent diffusion coefficient (ADC) values for bone marrow edema (BME), sclerosis area, fat deposit area, and normal-appearing bone marrow (NABM) (both patients and healthy volunteers) and the magnetization transfer (MT) rate of the cartilage (MTRc) were analyzed in the groups. The above five parameters (ADC (NABM), ADC (BME) and ADC (fat deposit) and MTRc) between the active group and the inactive group were compared. The effectiveness of each parameter in diagnosing sacroiliac arthritis of ankylosing spondylitis were analyzed, and the predictive value of the parameters was compared. Result: ADC(BME), ADC(NABM) and MTRc showed statistically significant differences between the active and inactive groups (P <0.05). ADC (BME) and ADC (NABM) could predict the activity of AS sacroiliac arthritis (P <0.01). ADC (NABM) and MTRc were significantly different between healthy volunteers and the active group (P <0.01). The areas under the ROC curve (AUCs) of ADC (BME)_ADC(NABM), ADC(NABM)_MTR, and ADC(BME)_MTRc were 0.885 (cut-off value=0.69), 0.849 (cut-off value=0.56) and 0.864 (cut-off value=0.60), respectively. The predictive ability of the combined index ADC (BME)_MTRc and ADC(NABM)_MTRc was increased. Conclusion: The ability to diagnose and predict AS might be improved by the combination of diffusion-weighted imaging (DWI) and magnetization transfer (MT).

Evaluation of amide proton transfer-weighted imaging for endometrial carcinoma histological features: a comparative study with diffusion kurtosis imaging.

OBJECTIVES: To investigate whether amide proton transfer-weighted imaging (APTWI) and diffusion kurtosis imaging (DKI) can be used to evaluate endometrial carcinoma (EC) in terms of clinical type, histological grade, subtype, and Ki-67 index. METHODS: Eighty-eight patients with EC underwent pelvic DKI and APTWI. The non-Gaussian diffusion coefficient (Dapp), apparent kurtosis coefficient (Kapp), and magnetization transfer ratio asymmetry (MTRasym (3.5 ppm)) were calculated and compared based on the clinical type (type I, II), histological grade (high- and low-grade), and subtype (endometrioid adenocarcinoma (EA) and non-EA). Correlation coefficients were calculated for each parameter with histological grades and the Ki-67 index. RESULTS: The MTRasym (3.5 ppm) and Kapp values were higher in the type II group and high-grade group than in the type I and low-grade groups, respectively, while the Dapp values were lower in the type I and low-grade groups, respectively (all p < 0.05). The Kapp value was higher in the EA group than in the non-EA group (p = 0.022). The Kapp value was the only independent predictor for the histological grade of EA and the clinical type of EC. The AUC (DKI) was higher than the AUC (APTWI) in the identification of type I and II EC and high- and low-grade EA (Z = 2.042, 2.013, p = 0.041, 0.044), while in the identification of EA and non-EA, only the difference in Kapp was statistically significant. Moreover, the Kapp and MTRasym (3.5 ppm) values and Dapp values correlated positively and negatively, respectively, with histological grade (r = 0.759, 0.555, 0.624, and 0.462, all p < 0.05) and Ki-67 index (r = -0.704, -0.507, all p < 0.05). CONCLUSION: Both DKI- and APTWI-related parameters have potential as imaging markers in estimating the histological features of EC, while DKI shows better performance than APTWI in this study. KEY POINTS: • DKI and APTWI can be used to preliminarily evaluate the histological characteristics of endometrial carcinoma (EC). • The Kapp was the only independent predictor for the histological grade of EA and the clinical type of EC. • The Kapp, MTRasym (3.5 ppm), and Dapp correlated positively and negatively, respectively, with histological grade and Ki-67 index.

Convergent effects of a functional C3 variant on brain atrophy, demyelination, and cognitive impairment in multiple sclerosis.

BACKGROUND: Complement system activation products are present in areas of neuroinflammation, demyelination, and neurodegeneration in brains of patients with multiple sclerosis (MS). C3 is a central element in the activation of complement cascades. A common coding variant in the C3 gene (rs2230199, C3R102G) affects C3 activity. OBJECTIVES: To assess the effects of rs2230199 on MS severity using clinical, cognitive, and imaging measures. METHODS: In total, 161 relapse-onset MS patients (Expanded Disability Status Scale (EDSS) ≤ 6) underwent physical assessments, cognitive tests (Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), and California Verbal Learning Test (CVLT)), and magnetic resonance imaging (MRI). Lesion volumes were quantified semi-automatically. Voxel-wise analyses were performed to assess the effects of rs2230199 genotype on gray matter (GM) atrophy ( n = 155), white matter (WM) fractional anisotropy (FA; n = 105), and WM magnetization transfer ratio (MTR; n = 90). RESULTS: While rs2230199 minor-allele dosage (C3-102G) showed no significant effect on EDSS and Multiple Sclerosis Functional Composite (MSFC), it was associated with worse cognitive performance ( p = 0.02), lower brain parenchymal fraction ( p = 0.003), and higher lesion burden ( p = 0.02). Moreover, voxel-wise analyses showed lower GM volume in subcortical structures and insula, and lower FA and MTR in several WM areas with higher copies of rs2230199 minor allele. CONCLUSION: C3-rs2230199 affects white and GM damage as well as cognitive impairment in MS patients. Our findings support a causal role for complement system activity in the pathophysiology of MS.

Testicular Apparent Diffusion Coefficient and Magnetization Transfer Ratio: Can These MRI Parameters Be Used to Predict Successful Sperm Retrieval in Nonobstructive Azoospermia?

OBJECTIVE. The aim of our study was to assess if testicular apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR) can be used as MRI parameters to predict the presence of spermatozoa retrieved after microdissection testicular sperm extraction (mTESE) in men with nonobstructive azoospermia (NOA). MATERIALS AND METHODS. The study included 49 men with NOA and 45 age-matched control subjects. Participants underwent scrotal MRI between June 2013 and January 2017, 1 day before mTESE. Testicular volume (TV), ADC, and MTR were measured. NOA testes were classified as follows: group 1, testes with higher Johnsen score of ≥ 8; and group 2, testes with higher Johnsen score of < 8. Nonparametric statistical tests were used to assess differences in TV, ADC, and MTR between men with NOA and control subjects, the two NOA groups, and NOA testes with positive sperm retrieval and NOA testes with negative sperm retrieval. RESULTS. TV (p < 0.001) was reduced and both ADC (p < 0.001) and MTR (p = 0.013) were increased in NOA testes compared with normal testes. A positive correlation between higher Johnsen score and TV (p < 0.001) and a negative correlation between higher Johnsen score and both ADC (p = 0.015) and MTR (p = 0.003) were found. TV (p < 0.001) was reduced in NOA testes with failed sperm retrieval compared with NOA testes with positive sperm retrieval. On the contrary, ADC (p = 0.011) and MTR (p = 0.045) were significantly increased in NOA testes with negative sperm retrieval. CONCLUSION. On the basis of our preliminary data, TV, ADC, and MTR might represent useful MRI parameters in the workup of patients with NOA by helping to predict the presence of spermatozoa after mTESE.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. KEY POINTS: • 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.

Normal testes asymmetry evaluated by apparent diffusion coefficient and magnetization transfer ratio.

Background In humans, the left testis generally hangs lower than the right and the right is larger than the left. Magnetic resonance imaging (MRI) represents an important adjuvant modality in the investigation of testicular diseases. Purpose To assess if normal testes asymmetry is related to apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR). Material and Methods The normal testes from 106 men were included. Testicular volume (TV) was calculated by using the ellipsoid formula: length × width × height × 0.52. Diffusion-weighted imaging was performed using a SS EPI diffusion pulse sequence and b-values of 0 and 900 s/mm-2. Magnetization transfer imaging was obtained using a 3D GRE sequence both with and without an off-resonance radiofrequency pulse. MTR maps were obtained by the following formula: (SIo-SIm) / (SIo) × 100%, where SIo and SIm represent the signal intensity in the baseline image and that in the corresponding image acquired with an off-resonance MT pulse, respectively. The mean and standard deviation of testicular volume (TV), ADC, and MTR of both testes was calculated and compared using a paired sample t-test. Results The mean TV (mL) was greater ( P = 0.006) for the right testis (16.77 ± 4.84) compared to the left (15.97 ± 4.45). ADC of the right testis (1.09 ± 0.12 × 10 - 3 mm2 s-1) was not different ( P = 0.064) from that of the left testis (1.07 ± 0.12 × 10-3 mm2 s-1). Differences ( P = 0.032) were observed between MTR of the right (46.6 ± 2.1%) and left testis (46.0 ± 2.2%). Conclusion The reported differences in paired testes size was confirmed, introducing a possible relationship with structural and functional asymmetry of normal testes, based on MTR.

Magnetization transfer imaging of normal and abnormal testis: preliminary results.

OBJECTIVES: The aim was to determine the magnetization transfer ratio (MTR) of normal testes, possible variations with age and to assess the feasibility of MTR in characterizing various testicular lesions. METHODS: Eighty-six men were included. A three-dimensional gradient-echo MT sequence was performed, with/without an on-resonance binomial prepulse. MTR was calculated as: (SIo-SIm)/(SIo) × 100 %, where SIm and SIo refers to signal intensities with and without the saturation pulse, respectively. Subjects were classified as: group 1, 20-39 years; group 2, 40-65 years; and group 3, older than 65 years of age. Analysis of variance (ANOVA) followed by the least significant difference test was used to assess variations of MTR with age. Comparison between the MTR of normal testis, malignant and benign testicular lesions was performed using independent-samples t testing. RESULTS: ANOVA revealed differences of MTR between age groups (F = 7.51, P = 0.001). Significant differences between groups 1, 2 (P = 0.011) and 1, 3 (P < 0.001) were found, but not between 2, 3 (P = 0.082). The MTR (in percent) of testicular carcinomas was 55.0 ± 3.2, significantly higher than that of benign lesions (50.3 ± 4.0, P = 0.02) and of normal testes (47.4 ± 2.2, P < 0.001). CONCLUSIONS: MTR of normal testes decreases with age. MTR might be helpful in the diagnostic work-up of testicular lesions. KEY POINTS: MTR of normal testes shows age-related changes. Testicular carcinomas have high MTR values. MTR may be useful in the diagnostic work-up of testicular lesions.

Glycosaminoglycan chemical exchange saturation transfer at 3T MRI in asymptomatic knee joints.

BACKGROUND: Biochemical alterations such as glycosaminoglycan (GAG) depletion occur early in the course of osteoarthritis, but cannot be detected with standard magnetic resonance techniques. With glycosaminoglycan chemical exchange saturation transfer (gagCEST), a biochemical imaging technique, it is feasible to detect biochemical components in knee joint cartilage. PURPOSE: To establish baseline values for gagCEST magnetic resonance imaging (MRI) in knee joint cartilage at 3 Tesla (T). MATERIAL AND METHODS: Twenty volunteers (8 women, 12 men; mean age, 24.55 ± 2.35 years;age range, 21-29 years) with no history or clinical findings indicative of knee joint pathologies underwent MRI at 3T. The imaging protocol included three-dimensional (3D) double-echo steady-state sequence for morphological cartilage assessment and a prototype 3D CEST pulse sequence to evaluate the CEST effects in six cartilage regions of the knee joint: (i) lateral femoral condyle; (ii) medial femoral condyle; (iii) lateral tibial plateau; (iv) medial tibial plateau; (v) patella; and (vi) trochlea. We used the asymmetry of the magnetization transfer ratio (MTRasym) parameter to quantify the gagCEST effects in these regions. RESULTS: Regional differences revealed high MTRasym values in the patellar (1.62% ± 1.19%) and the trochlear (1.17% ± 1.29%) cartilages, and low MTRasym values in the medial femoral condyle (0.41% ± 0.58%) and the lateral tibial plateau (0.52% ± 0.53%) cartilages. CONCLUSION: Regional differences in the gagCEST values must be considered when conducting gagCEST imaging of knee joint cartilage. In the future gagCEST imaging may be an additional feature in the evaluation of the biochemical composition of knee joint cartilage.

The role of diffusion-weighted MRI and contrast-enhanced MRI for differentiation between solid renal masses and renal cell carcinoma subtypes.

PURPOSE: To assess the value of diffusion-weighted magnetic resonance imaging (DW-MRI) and contrast-enhanced MRI (CE-MRI) for differentiation between benign and malignant solid renal masses, renal cell carcinoma (RCC) subtypes, oncocytomas, and lipid-poor angiomyolipomas (LP-AML). METHODS: Minimum or lowest 'apparent diffusion coefficient' (ADC1) and representative ADC values (ADC2) of 112 renal masses (n: 46 benign renal mass, n: 66 malignant renal mass) were measured on DW-MRI images (b 50, 400, 800 s/mm2). Signal intensity (SI) measurements were performed in normal renal parenchyma and most avid enhanced area of the renal masses at precontrast, corticomedullary, and nephrographic phases on CE-MRI. Contrast enhancement rate (CER) and contrast enhancement index (CEI) values of renal masses were compared between benign-malignant renal masses and RCC subtypes, oncocytomas, and LP-AMLs. RESULTS: There was no significant difference between ADC1, ADC2 values, and SI of benign and malignant renal masses (p = 0.721, p = 0.255, p = 0.872). Mean ADC1 and ADC2 values of clear cell RCCs were significantly higher than nonclear cell RCCs (p = 0.005 p = 0.002). Mean CER value of clear cell RCCs was significantly higher than nonclear cell RCCs in nephrographic phase (p = 0.003). Mean CEI values of clear cell RCCs were significantly higher than nonclear cell RCCs in the corticomedullary and nephrographic phase (p = 0.027 vs. 0.008). LP-AMLs were differentiated from other renal masses with wash-out phenomenon. CONCLUSION: Combined usage of ADC, SI, CER, and CEI values may be useful for discrimination between RCC subtypes, oncocytomas, and lipid-poor AMLs.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Magnetization transfer contrast MRI in GFP­tagged 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, non­invasive 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.

High-resolution magnetization transfer MRI in patients with cervical spondylotic myelopathy.

Magnetization transfer (MT) contrast has been established as a marker of myelin integrity, and cervical spondylotic myelopathy is known to cause demyelination. Ten patients with clinical and magnetic resonance imaging (MRI) manifestations of cervical spondylotic myelopathy (CSM) were compared to the MRIs of seven historic healthy controls, using the magnetization transfer ratio (MTR) and Nurick scores as the primary metrics. Transverse slices through the intervertebral discs of the cervical spine were acquired using a gradient echo sequence (MEDIC) with and without an MT saturation pulse on a 3 Tesla Siemens Prisma scanner (TR = 300 ms, TEeff = 17 ms, flip angle = 30°, in-plane resolution = 0.47 × 0.47 mm2). The CSM patients tended to have a lower mean MTR (30.4 ±â€¯6.5) than the controls (34.8 ±â€¯3.8), but the difference was not significant (independent samples t-test, p = 0.110, Cohen's d = 0.80). The mean MTR across all intervertebral disc levels was not significantly correlated to the Nurick score (Spearman's ρ = -0.489, p = 0.151). The intervertebral level with the lowest MTR in each cohort was not significantly different between groups (equal variances not assumed, t = 1.965, dof = 14.8, p = 0.068, Cohen's d = 0.88), but the CSM patients tended to have a lower MTR. The mean MTR at this level was negatively correlated to the Nurick score among CSM patients (Spearman's ρ = -0.725, p = 0.018). CSM patients tended to have decreased MTR indicating myelin degradation compared to our healthy subjects, and MTR was negatively correlated with the severity of CSM.

Olfactory Impairment in Parkinson's Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging.

BACKGROUND: Olfactory impairment is an early manifestation of Parkinson's disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter. OBJECTIVE: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT. METHODS: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions. RESULTS: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls. CONCLUSIONS: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.

Assessment of the patellofemoral cartilage: Correlation of knee pain score with magnetic resonance cartilage grading and magnetization transfer ratio asymmetry of glycosaminoglycan chemical exchange saturation transfer.

PURPOSE: Biochemical imaging of glycosaminoglycan chemical exchange saturation transfer (gagCEST) could predict the depletion of glycosaminoglycans (GAG) in early osteoarthritis. The purpose of this study was to evaluate the relationship between the magnetization transfer ratio asymmetry (MTRasym) of gagCEST images and visual analog scale (VAS) pain scores in the knee joint. MATERIALS AND METHODS: This retrospective study was approved by the institutional review board. A phantom study was performed using hyaluronic acid to validate the MTRasym values of gagCEST images. Knee magnetic resonance (MR) images of 22 patients (male, 9; female, 13; mean age, 50.3years; age range; 25-79years) with knee pain were included in this study. The MR imaging (MRI) protocol involved standard knee MRI as well as gagCEST imaging, which allowed region-of-interest analyses of the patellar facet and femoral trochlea. The MTRasym at 1.0ppm was calculated at each region. The cartilages of the patellar facets and femoral trochlea were graded according to the Outerbridge classification system. Data regarding the VAS scores of knee pain were collected from the electronic medical records of the patients. Statistical analysis was performed using Spearman's correlation. RESULTS: The results of the phantom study revealed excellent correlation between the MTRasym values and the concentration of GAGs (r=0.961; p=0.003). The cartilage grades on the MR images showed significant negative correlation with the MTRasym values in the patellar facet and femoral trochlea (r=-0.460; p=0.031 and r=-0.543; p=0.009, respectively). The VAS pain scores showed significant negative correlation with the MTRasym values in the patellar facet and femoral trochlea (r=-0.435; p=0.043 and r=-0.671; p=0.001, respectively). CONCLUSION: The pain scores were associated with the morphological and biochemical changes in articular cartilages visualized on knee MR images. The biochemical changes, visualized in terms of the MTRasym values of the gagCEST images, exhibited greater correlation with the pain scores than the morphological changes visualized on conventional MR images; these results provide evidence supporting the theory regarding the association of patellofemoral osteoarthritis with knee pain scores.

Magnetic resonance imaging findings of cellular angiofibroma of the tunica vaginalis of the testis: a case report.

BACKGROUND: Cellular angiofibroma represents a rare mesenchymal tumor typically involving the inguinoscrotal area in middle-aged men. Although the origin of this benign tumor is unknown, it is histologically classified as an angiomyxoid tumor. Cellular angiofibroma is characterized by a diversity of pathological and imaging features. An accurate preoperative diagnosis is challenging. Magnetic resonance imaging examination of the scrotum has been reported as a valuable adjunct modality in the investigation of scrotal pathology. The technique by providing both structural and functional information is useful in the differentiation between extratesticular and intratesticular diseases and in the preoperative characterization of the histologic nature of various scrotal lesions. There are few reports in the English literature addressing the magnetic resonance imaging findings of cellular angiofibroma of the scrotum and no reports on functional magnetic resonance imaging data. Here we present the first case of a cellular angiofibroma arising from the tunica vaginalis of the testis and we discuss the value of a multiparametric magnetic resonance protocol, including diffusion-weighted imaging, magnetization transfer imaging and dynamic contrast-enhanced magnetic resonance imaging in the preoperative diagnosis of this rare neoplasm. CASE PRESENTATION: A 47-year Greek man presented with a painless left scrotal swelling, which had gradually enlarged during the last 6 months. Magnetic resonance imaging of his scrotum displayed a left paratesticular mass, in close proximity to the tunica vaginalis, with heterogeneous high signal intensity on T2-weighted images and no areas of restricted diffusion. The tumor was hypointense on magnetization transfer images, suggestive for the presence of macromolecules. On dynamic contrast-enhanced magnetic resonance imaging the mass showed intense heterogeneous enhancement with a type II curve. Magnetic resonance imaging findings were strongly suggestive of a benign paratesticular tumor, which was confirmed on pathology following lesion excision. CONCLUSIONS: Magnetic resonance imaging of the scrotum by combining conventional and functional magnetic resonance data provides useful diagnostic information in the preoperative characterization of scrotal masses. A possible diagnosis of a benign paratesticular tumor based on magnetic resonance imaging features may improve patient care and decrease the number of unnecessary radical surgical explorations.

Chronic T2 Lesions in Multiple Sclerosis are Heterogeneous Regarding Phase MR Imaging.

PURPOSE: Phase imaging provides additional information on multiple sclerosis (MS) lesions and may in combination with mean diffusivity (MD) and magnetization transfer ratio (MTR) help differentiating heterogeneity of MS lesion pathology. METHODS: Magnetic resonance imaging (MRI) was performed in 23 MS patients including diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), and SWI. Mean values (MTR, MD, and homodyne filtered phase) from 138 chronic MS lesions and normal appearing white matter (NAWM) were obtained and correlations examined. For explorative analysis, a divisive hierarchical clustering algorithm was applied. RESULTS: Phase characteristics were an independent characteristic of chronic T2 lesions, as MTR and MD were not correlated with phase values (R = - 0.23, R = - 0.18). Dependent on MTR, MD, and phase, cluster analysis led to five lesion groups. Of the two groups with phase values close to NAWM, one presented with highest MD and most severe MTR decrease (p = 0.01), the other with slight MD increase and MTR decrease. Two lesion groups with highest phase values (p = 0.01) displayed slightly increased MD and moderate decrease in MTR. Clinical data including EDSS, disease duration, and age did not differ significantly between groups. CONCLUSIONS: Increased phase is predominantly detectable in lesions with clear MTR decrease but only moderate MD increase. Phase images seem to represent an independent parameter for MS lesion characterization and may provide additional information on MS lesion heterogeneity.

Cardio-chemical exchange saturation transfer magnetic resonance imaging reveals molecular signatures of endogenous fibrosis and exogenous contrast media.

BACKGROUND: Application of emerging molecular MRI techniques, including chemical exchange saturation transfer (CEST)-MRI, to cardiac imaging is desirable; however, conventional methods are poorly suited for cardiac imaging, particularly in small animals with rapid heart rates. We developed a CEST-encoded steady state and retrospectively gated cardiac cine imaging sequence in which the presence of fibrosis or paraCEST contrast agents was directly encoded into the steady-state myocardial signal intensity (cardioCEST). METHODS AND RESULTS: Development of cardioCEST: A CEST-encoded cardiac cine MRI sequence was implemented on a 9.4T small animal scanner. CardioCEST of fibrosis was serially performed by acquisition of a series of CEST-encoded cine images at multiple offset frequencies in mice (n=7) after surgically induced myocardial infarction. Scar formation was quantified using a spectral modeling approach and confirmed with histological staining. Separately, circulatory redistribution kinetics of the paramagnetic CEST agent Eu-HPDO3A were probed in mice using cardioCEST imaging, revealing rapid myocardial redistribution, and washout within 30 minutes (n=6). Manipulation of vascular tone resulted in heightened peak CEST contrast in the heart, but did not alter redistribution kinetics (n=6). At 28 days after myocardial infarction (n=3), CEST contrast kinetics in infarct zone tissue were altered, demonstrating gradual accumulation of Eu-HPDO3A in the increased extracellular space. CONCLUSIONS: cardioCEST MRI enables in vivo imaging of myocardial fibrosis using endogenous contrast mechanisms, and of exogenously delivered paraCEST agents, and can enable multiplexed imaging of multiple molecular targets at high-resolution coupled with conventional cardiac MRI scans.

Imaging of Primary Brain Tumors and Metastases with Fast Quantitative 3-Dimensional Magnetization Transfer.

BACKGROUND AND PURPOSE: This study assesses whether magnetization transfer (MT) imaging provides additive information to conventional MRI in brain tumors. METHODS: MT data of 26 patients with neoplastic and metastatic brain tumors were analyzed at 1.5 T. For the 3 largest tumor groups investigated in this study--glioblastoma multiforme (GBM), meningiomas, and metastases-statistical comparisons were performed. Analyzed MT parameters included the magnetization transfer ratio (MTR) and 4 quantitative MT parameters (qMT): Relaxation times (T1, T2), exchange rate (kf), and macromolecular content (F). Total imaging time of high-resolution whole brain MTR and qMT imaging with balanced steady-state free precession required 9 minutes. Five ROIs were chosen: Contrast-enhancing (T1W-CE), noncontrast-enhancing (T1W-non-CE), proximal hyperintensity (T2W-pSI), distal hyperintensity (T2W-dSI), and a reference (ref). RESULTS: Pathologies showed significant (P < .05) MT changes (MTR and qMT) compared to the reference. The T1W-CE, T1W-non-CE, and T2W-pSI ROIs of GBMs, meningiomas, and metastases showed significant differences in MTR and qMT estimates. Similar MTR with significant different qMT values were observed in several ROIs among different lesions. MT maps (MTR and qMT) indicated changes in tissue appearing unaffected on MRI in most glial tumors. CONCLUSIONS: MTR and qMT imaging enables a better differentiation between brain tumors and provides additive information to MRI.