Benjamin Schmitt

Cartilage Quality Assessment by Using Glycosaminoglycan Chemical Exchange Saturation Transfer and 23Na MR Imaging at 7 T

PURPOSE To compare a glycosaminoglycan chemical exchange saturation transfer (gagCEST) imaging method, which enables sampling of the water signal as a function of the presaturation offset (z-spectrum) at 13 points in clinically feasible imaging times, with sodium 23 ((23)Na) magnetic resonance (MR) imaging in patients after cartilage repair surgery (matrix-associated autologous chondrocyte transplantation and microfracture therapy). MATERIALS AND METHODS One female patient (67.3 years), and 11 male patients (median age, 28.8 years; interquartile range [IQR], 24.6-32.3 years) were examined with a 7-T whole-body system, with approval of the local ethics committee after written informed consent was obtained. A modified three-dimensional gradient-echo sequence and a 28-channel knee coil were used for gagCEST imaging. (23)Na imaging was performed with a circularly polarized knee coil by using a modified gradient-echo sequence. Statistical analysis of differences and Spearman correlation were applied. RESULTS The median of asymmetries in gagCEST z-spectra summed over all offsets from 0 to 1.3 ppm was 7.99% (IQR, 6.33%-8.79%) in native cartilage and 5.13% (IQR, 2.64%-6.34%) in repair tissue. A strong correlation (r = 0.701; 95% confidence interval: 0.21, 0.91) was found between ratios of signal intensity from native cartilage to signal intensity from repair tissue obtained with gagCEST or (23)Na imaging. The median of dimensionless ratios between native cartilage and repair tissue was 1.28 (IQR, 1.20-1.58) for gagCEST and 1.26 (IQR, 1.21-1.48) for (23)Na MR imaging. CONCLUSION The high correlation between the introduced gagCEST method and (23)Na imaging implies that gagCEST is a potentially useful biomarker for glycosaminoglycans.

Relaxation-compensated CEST-MRI of the human brain at 7T: Unbiased insight into NOE and amide signal changes in human glioblastoma

Endogenous chemical exchange saturation transfer (CEST) effects of protons resonating near to water protons are always diluted by competing effects such as direct water saturation and semi-solid magnetization transfer (MT). This leads to unwanted T2 and MT signal contributions that contaminate the observed CEST signal. Furthermore, all CEST effects appear to be scaled by the T1 relaxation time of the mediating water pool. As MT, T1 and T2 are also altered in tumor regions, a recently published correction algorithm yielding the apparent exchange-dependent relaxation AREX, is used to evaluate in vivo CEST effects. This study focuses on CEST effects of amides (3.5ppm) and Nuclear-Overhauser-mediated saturation transfer (NOE, -3.5ppm) that can be properly isolated at 7T. These were obtained in 10 glioblastoma patients, and this is the first comprehensive study where AREX is applied in human brain as well as in human glioblastoma. The correction of CEST effects alters the contrast significantly: after correction, the CEST effect of amides does not show significant contrast between contrast enhancing tumor regions and normal tissue, whereas NOE drops significantly in the tumor area. In addition, new features in the AREX contrasts are visible. This suggests that previous CEST approaches might not have shown pure CEST effects, but rather water relaxation shine-through effects. Our insights help to improve understanding of the CEST effect changes in tumors and correlations on a cellular and molecular level.

Pilot study of Iopamidol-based quantitative pH imaging on a clinical 3T MR scanner

ObjectiveThe objective of this study was to show the feasibility to perform Iopamidol-based pH imaging via clinical 3T magnetic resonance imaging (MRI) using chemical exchange saturation transfer (CEST) imaging with pulse train presaturation.Materials and methodsThe pulse train presaturation scheme of a CEST sequence was investigated for Iopamidol-based pH measurements using a 3T magnetic resonance (MR) scanner. The CEST sequence was applied to eight tubes filled with 100-mM Iopamidol solutions with pH values ranging from 5.6 to 7.0. Calibration curves for pH quantification were determined. The dependence of pH values on the concentration of Iopamidol was investigated. An in vivo measurement was performed in one patient who had undergone a previous contrast-enhanced computed tomography (CT) scan with Iopamidol. The pH values of urine measured with CEST MRI and with a pH meter were compared.ResultsIn the measured pH range, pH imaging using CEST imaging with pulse train presaturation was possible. Dependence between the pH value and the concentration of Iopamidol was not observed. In the in vivo investigation, the pH values in the human bladder measured by the Iopamidol CEST sequence and in urine were consistent.ConclusionOur study shows the feasibility of using CEST imaging with Iopamidol for quantitative pH mapping in vitro and in vivo on a 3T MR scanner.

Age-dependency of glycosaminoglycan content in lumbar discs: A 3t gagcEST study

To analyze age‐dependency of glycosaminoglycan content using gagCEST (glycosaminoglycan chemical exchange saturation transfer) imaging in lumbar intervertebral discs of healthy volunteers.

Glycosaminoglycan chemical exchange saturation transfer of lumbar intervertebral discs in patients with spondyloarthritis

To assess glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVD) in patients with spondyloarthritis (SpA) using glycosaminoglycan chemical exchange saturation transfer (gagCEST).

Gender, BMI and T2 dependencies of glycosaminoglycan chemical exchange saturation transfer in intervertebral discs

PURPOSE The purpose was to investigate the dependence of glycosaminoglycan chemical exchange saturation transfer (gagCEST) effect of lumbar intervertebral discs (IVD) on gender, body mass index and T2 value. METHODS T2 imaging and gagCEST imaging was performed in 34 healthy volunteers (17 males, 17 females) without low back pain at a 3T MRI system (Magnetom Trio, A Tim System, Siemens Healthcare, Erlangen, Germany). The body mass index was determined for each volunteer. The mean and standard deviation of MTRasym and T2 values were calculated for nucleus pulposus (NP) and annulus fibrosus (AF) as descriptive statistics for females and males. An unpaired students t-test was applied in order to validate obtained differences. Pearson correlation was determined in order to reveal, if gagCEST effect and T2 values decrease with increasing body mass index (BMI). Pearson correlation analysis was additionally performed between gagCEST and T2 values. RESULTS GagCEST effect and T2 values were significantly higher in females compared to males [gagCEST effect (nucleus pulposus, females)=3.58±1.49%; gagCEST effect (nucleus pulosus, males)=3.01±1.63%, p-value (gagCEST effect, nucleus pulposus)=0.02); T2 (nucleus pulposus, females)=134.56±30.27 ms, T2 (nucleus pulposus, males)=122.35±27.64 ms, p-value (T2, nucleus pulposus)=0.01)]. Pearson correlation analysis showed a significant negative relation between BMI and gagCEST effect (nucleus pulposus: ρ=-0.16, p=0.03) and between BMI and T2 values (nucleus pulposus: ρ=-0.30, p<0.01). The correlation between gagCEST effect and T2-values was highly significant (nucleus pulposus: ρ=0.59, p<0.01). CONCLUSIONS Significantly lower gagCEST effects were found in males compared to females and with increased body mass index. The gagCEST effect was highly correlated with quantitative T2 imaging.

Comparison of Routine Brain Imaging at 3 T and 7 T.

ObjectiveThe aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], image quality, diagnostic confidence) from a standard brain magnetic resonance imaging examination encompassing common neurological disorders such as demyelinating disease, gliomas, cerebrovascular disease, and epilepsy, with comparable sequence protocols and acquisition times at 3 T and at 7 T. Materials and MethodsTen healthy volunteers and 4 subgroups of 40 patients in total underwent comparable magnetic resonance protocols with standard diffusion-weighted imaging, 2D and 3D turbo spin echo, 2D and 3D gradient echo and susceptibility-weighted imaging of the brain (10 sequences) at 3 T and 7 T. The subgroups comprised patients with either lesional (n = 5) or nonlesional (n = 4) epilepsy, intracerebral tumors (n = 11), demyelinating disease (n = 11) (relapsing-remitting multiple sclerosis [MS, n = 9], secondary progressive MS [n = 1], demyelinating disease not further specified [n = 1]), or chronic cerebrovascular disorders [n = 9]). For quantitative analysis, SNR and CNR were determined. For a semiquantitative assessment of the diagnostic confidence, a 10-point scale diagnostic confidence score (DCS) was applied. Two experienced radiologists with additional qualification in neuroradiology independently assessed, blinded to the field strength, 3 pathology-specific imaging criteria in each of the 4 disease groups and rated their diagnostic confidence. The overall image quality was semiquantitatively assessed using a 4-point scale taking into account whether diagnostic decision making was hampered by artifacts or not. ResultsWithout correction for spatial resolution, SNR was higher at 3 T except in the T2 SPACE 3D, DWI single shot, and DIR SPACE 3D sequences. The SNR corrected by the ratio of 3 T/7 T voxel sizes was higher at 7 T than at 3 T in 10 of 11 sequences (all except for T1 MP2RAGE 3D).In CNR, there was a wide variation between sequences and patient cohorts, but average CNR values were broadly similar at 3 T and 7 T.DCS values for all 4 pathologic entities were higher at 7 T than at 3 T. The DCS was significantly higher at 7 T for diagnosis and exclusion of cortical lesions in vascular disease. A tendency to higher DCS at 7 T for cortical lesions in MS was observed, and for the depiction of a central vein and iron deposits within MS lesions. Despite motion artifacts, DCS values were higher at 7 T for the diagnosis and exclusion of hippocampal sclerosis in mesial temporal lobe epilepsy (improved detection of the hippocampal subunits). Interrater agreement was 69.7% at 3 T and 93.3% at 7 T. There was no significant difference in the overall image quality score between 3 T and 7 T taking into account whether diagnostic decision making was hampered by artifacts or not. ConclusionsUltra–high-field magnetic resonance imaging at 7 T compared with 3 T yielded an improved diagnostic confidence in the most frequently encountered neurologic disorders. Higher spatial resolution and contrast were identified as the main contributory factors.

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.

Glycosaminoglycan Chemical Exchange Saturation Transfer of Lumbar Intervertebral Discs in Healthy Volunteers.

Study Design. Evaluation of a new quantitative imaging technique in a prospective study design. Objective. To assess glycosaminoglycan (GAG) content of lumbar intervertebral discs (IVDs) in healthy volunteers with chemical exchange saturation transfer (CEST). Summary of Background Data. Biochemical alterations of lumbar discs are present before the appearance of morphological changes. GAG loss plays a central role in these degenerative processes. Methods. Lumbar intervertebral discs of healthy controls (26 women, 22 men; mean age 31 ± 8 years; range: 21–49 years) without lumbar back pain were examined at a 3 Tesla magnetic resonance imaging (MRI) scanner in this prospective study. None of the participants were overweight or had previous surgery of the lumbar spine. The MRI protocol included standard morphological, sagittal and transversal T2-weighted (T2w) images to assess Pfirrmann score and to detect disc disorders according to the Combined Task Force classification of five lumbar IVDs (L1 to S1). A prototype glycosaminoglycan chemical exchange saturation transfer (gagCEST) sequence was applied to measure GAG content of the nucleus pulposus (NP) and annulus fibrosus (AF) by identifying the magnetization transfer asymmetry ratio (MTRasym) in a region-of-interest analysis. Morphological and biochemical imaging analysis were statistically tested for quantitative differences between different grades of IVD degeneration and disc disorders. Results. gagCEST values of NP demonstrated a significant negative correlation with morphological Pfirrmann score (r = −0.562; P < 0.0001). The MTRasym values were higher in non-degenerative lumbar IVDs (Pfirrmann 1–2) compared with degenerative lumbar discs (Pfirrmann 3–5; 2.92% ± 1.42% vs. 0.78% ± 1.38%; P < 0.0001). The MTRasym values of NP were significantly higher in normal appearing discs compared with herniated IVDs (2.83% ± 1.52% vs. 1.55% ± 1.61%; P < 0.0001). We found a significant negative correlation between gagCEST values and the graduation of disc herniation (r = −0.372; P < 0.0001). Conclusion. Biochemical imaging with gagCEST distinguished morphologically degenerative from non-degenerative lumbar IVDs (in NP and AF) of healthy volunteers at a clinical 3T-MRI system. The depletion of GAG content in degenerative lumbar discs correlated significantly with the morphological disc classification. We could demonstrate that disc disorders, such as protrusion and extrusion, were accompanied by lower GAG content. Level of Evidence: 2

Exercise cardiac MRI-derived right ventriculo-arterial coupling ratio detects early right ventricular maladaptation in PAH.

Exercise intolerance and right ventricular (RV) dysfunction are cardinal features of pulmonary arterial hypertension (PAH). Despite the significantly elevated afterload, patients rarely experience symptoms at rest until the late stages of the disease. Recent data suggest that the ability of the right ventricle to adapt to increased afterload is an important determinant of exercise capacity and outcome in PAH [1]. RV ejection fraction (RVEF) has been demonstrated to predict outcome [2]. There is also growing evidence that a noninvasively derived right ventriculo-arterial coupling ratio (VACR) may provide important prognostic information [3]. However, it remains unclear to what extent RV contractility is impaired during exercise and which metric best describes ventricular functional adaptation to afterload in PAH. We aimed to evaluate and compare the effects of submaximal exercise on RV systolic function and VACR in PAH and healthy subjects using cardiac magnetic resonance (MRI). We also examined and compared VACR and cardiopulmonary exercise test (CPET) in estimating the severity of disease. In well-compensated PAH, early RV maladaptation is best captured by changes in SV/ESV at exercise by cardiac MRI http://ow.ly/MyEi302UUeL