CEST MRI provides amide/amine surrogate biomarkers for treatment-naïve glioma sub-typing.

PURPOSE: Accurate glioma classification affects patient management and is challenging on non- or low-enhancing gliomas. This study investigated the clinical value of different chemical exchange saturation transfer (CEST) metrics for glioma classification and assessed the diagnostic effect of the presence of abundant fluid in glioma subpopulations. METHODS: Forty-five treatment-naïve glioma patients with known isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion status received CEST MRI (B1rms = 2µT, Tsat = 3.5 s) at 3 T. Magnetization transfer ratio asymmetry and CEST metrics (amides: offset range 3-4 ppm, amines: 1.5-2.5 ppm, amide/amine ratio) were calculated with two models: 'asymmetry-based' (AB) and 'fluid-suppressed' (FS). The presence of T2/FLAIR mismatch was noted. RESULTS: IDH-wild type had higher amide/amine ratio than IDH-mutant_1p/19qcodel (p < 0.022). Amide/amine ratio and amine levels differentiated IDH-wild type from IDH-mutant (p < 0.0045) and from IDH-mutant_1p/19qret (p < 0.021). IDH-mutant_1p/19qret had higher amides and amines than IDH-mutant_1p/19qcodel (p < 0.035). IDH-mutant_1p/19qret with AB/FS mismatch had higher amines than IDH-mutant_1p/19qret without AB/FS mismatch ( < 0.016). In IDH-mutant_1p/19qret, the presence of AB/FS mismatch was closely related to the presence of T2/FLAIR mismatch (p = 0.014). CONCLUSIONS: CEST-derived biomarkers for amides, amines, and their ratio can help with histomolecular staging in gliomas without intense contrast enhancement. T2/FLAIR mismatch is reflected in the presence of AB/FS CEST mismatch. The AB/FS CEST mismatch identifies glioma subgroups that may have prognostic and clinical relevance.

Assessment of Amide proton transfer weighted (APTw) MRI for pre-surgical prediction of final diagnosis in gliomas.

PURPOSE: Radiological assessment of primary brain neoplasms, both high (HGG) and low grade tumors (LGG), based on contrast-enhancement alone can be inaccurate. We evaluated the radiological value of amide proton transfer weighted (APTw) MRI as an imaging complement for pre-surgical radiological diagnosis of brain tumors. METHODS: Twenty-six patients were evaluated prospectively; (22 males, 4 females, mean age 55 years, range 26-76 years) underwent MRI at 3T using T1-MPRAGE pre- and post-contrast administration, conventional T2w, FLAIR, and APTw imaging pre-surgically for suspected primary/secondary brain tumor. Assessment of the additional value of APTw imaging compared to conventional MRI for correct pre-surgical brain tumor diagnosis. The initial radiological pre-operative diagnosis was based on the conventional contrast-enhanced MR images. The range, minimum, maximum, and mean APTw signals were evaluated. Conventional normality testing was performed; with boxplots/outliers/skewness/kurtosis and a Shapiro-Wilk's test. Mann-Whitney U for analysis of significance for mean/max/min and range APTw signal. A logistic regression model was constructed for mean, max, range and Receiver Operating Characteristic (ROC) curves calculated for individual and combined APTw signals. RESULTS: Conventional radiological diagnosis prior to surgery/biopsy was HGG (8 patients), LGG (12 patients), and metastasis (6 patients). Using the mean and maximum: APTw signal would have changed the pre-operative evaluation the diagnosis in 8 of 22 patients (two LGGs excluded, two METs excluded). Using a cut off value of >2.0% for mean APTw signal integral, 4 of the 12 radiologically suspected LGG would have been diagnosed as high grade glioma, which was confirmed by histopathological diagnosis. APTw mean of >2.0% and max >2.48% outperformed four separate clinical radiological assessments of tumor type, P-values = .004 and = .002, respectively. CONCLUSIONS: Using APTw-images as part of the daily clinical pre-operative radiological evaluation may improve diagnostic precision in differentiating LGGs from HGGs, with potential improvement of patient management and treatment.

Multiple interleaved mode saturation (MIMOSA) for B1+ inhomogeneity mitigation in chemical exchange saturation transfer.

PURPOSE: To mitigate B1+ inhomogeneity in quantitative CEST MRI at ultra-high magnetic field strengths (B0 ≥ 7 Tesla) using a parallel transmit system. METHODS: Multiple interleaved mode saturation employs interleaving of 2 complementary phase sets during the saturation pulse train. Phase differences of 45° (first mode) and 90° (second mode) between 2 adjacent transmitter coil channels are used. The influence of the new saturation scheme on the CEST contrast was analyzed using Bloch-McConnell simulations. The presented method was verified in phantom and in vivo measurements of the healthy human brain. The relayed nuclear Overhauser effect was evaluated, and the inverse magnetic transfer ratio metric was calculated. Results were compared to a published B1+ correction method. All measurements were conducted on a whole-body 7 Tesla MRI system using an 8 transmitter and 32 receiver channel head coil. RESULTS: Simulations showed that the inverse magnetic transfer ratio metric contrast of relayed nuclear Overhauser effect shows a smaller dependency on the relative amplitudes of the 2 different modes than the contrasts of Cr and amide proton transfer. Measurements of an egg white phantom showed markedly improved homogeneity compared to the uncorrected inverse magnetic transfer ratio metric (relayed nuclear Overhauser effect) images and slightly improved results compared to B1+ corrected images. In vivo multiple interleaved mode saturation images showed similar contrast compared to B1+ corrected images. CONCLUSION: Multiple interleaved mode saturation can be used as a simple method to mitigate B1+ inhomogeneity effects in CEST MRI at ultra-high magnetic field strengths. Compared to previous B1+ correction methods, acquisition time can be reduced because an additional scan, usually required for B1+ correction, can be omitted.

A comparison of static and dynamic ∆B0 mapping methods for correction of CEST MRI in the presence of temporal B0 field variations.

PURPOSE: To assess the performance, in the presence of scanner instabilities, of three dynamic correction methods which integrate ∆B0 mapping into the chemical exchange saturation transfer (CEST) measurement and three established static ∆B0 -correction approaches. METHODS: A homogeneous phantom and five healthy volunteers were scanned with a CEST sequence at 7 T. The in vivo measurements were performed twice: first with unaltered system frequency and again applying frequency shifts during the CEST acquisition. In all cases, retrospective voxel-wise ∆B0 -correction was performed using one intrinsic and two extrinsic [prescans with dual-echo gradient-echo and water saturation shift referencing (WASSR)] static approaches. These were compared with two intrinsic [using phase data directly generated by single-echo or double-echo GRE (gradient-echo) CEST readout (CEST-GRE-2TE)] and one extrinsic [phase from interleaved dual-echo EPI (echo planar imaging) navigator (NAV-EPI-2TE)] dynamic ∆B0 -correction approaches [allowing correction of each Z-spectral point before magnetization transfer ratio asymmetry (MTRasym) analysis]. RESULTS: All three dynamic methods successfully mapped the induced drift. The intrinsic approaches were affected by the CEST labeling near water (∆ω < |0.3| ppm). The MTRasym contrast was distorted by the frequency drift in the brain by up to 0.21%/Hz when static ∆B0 -corrections were applied, whereas the dynamic ∆B0 corrections reduced this to <0.01%/Hz without the need of external scans. The CEST-GRE-2TE and NAV-EPI-2TE resulted in highly consistent MTRasym values with/without drift for all subjects. CONCLUSION: Reliable correction of scanner instabilities is essential to establish clinical CEST MRI. The three dynamic approaches presented improved the ∆B0 -correction performance significantly in the presence of frequency drift compared to established static methods. Among them, the self-corrected CEST-GRE-2TE was the most accurate and straightforward to implement.

Chemical exchange saturation transfer imaging in hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common complication in liver cirrhosis and associated with an invasion of ammonia into the brain through the blood-brain barrier. Resulting higher ammonia concentrations in the brain are suggested to lead to a dose-dependent gradual increase of HE severity and an associated impairment of brain function. Amide proton transfer-weighted (APTw) chemical exchange saturation transfer (CEST) imaging has been found to be sensitive to ammonia concentration. The aim of this work was to study APTw CEST imaging in patients with HE and to investigate the relationship between disease severity, critical flicker frequency (CFF), psychometric test scores, blood ammonia, and APTw signals in different brain regions. Whole-brain APTw CEST images were acquired in 34 participants (14 controls, 20 patients (10 minimal HE, 10 manifest HE)) on a 3 T clinical MRI system accompanied by T1 mapping and structural images. T1 normalized magnetization transfer ratio asymmetry analysis was performed around 3 ppm after B0 and B1 correction to create APTw images. All APTw images were spatially normalized into a cohort space to allow direct comparison. APTw images in 6 brain regions (cerebellum, occipital cortex, putamen, thalamus, caudate, white matter) were tested for group differences as well as the link to CFF, psychometric test scores, and blood ammonia. A decrease in APTw intensities was found in the cerebellum and the occipital cortex of manifest HE patients. In addition, APTw intensities in the cerebellum correlated positively with several psychometric scores, such as the fine motor performance scores MLS1 for hand steadiness / tremor (r = 0.466; p = .044) and WRT2 for motor reaction time (r = 0.523; p = .022). Moreover, a negative correlation between APTw intensities and blood ammonia was found for the cerebellum (r = -0.615; p = .007) and the occipital cortex (r = -0.478; p = .045). An increase of APTw intensities was observed in the putamen of patients with minimal HE and correlated negatively with the CFF (r = -0.423; p = .013). Our findings demonstrate that HE is associated with regional differential alterations in APTw signals. These variations are most likely a consequence of hyperammonemia or hepatocerebral degeneration processes, and develop in parallel with disease severity.

Ammonia-weighted imaging by chemical exchange saturation transfer MRI at 3 T.

Hepatic encephalopathy (HE) is triggered by liver cirrhosis and is associated with an increased ammonia level within the brain tissue. The goal of this study was to investigate effects of ammonia on in vitro amide proton transfer (APT)-weighted chemical exchange saturation transfer (CEST) imaging in order to develop an ammonia-sensitive brain imaging method. APT-weighted CEST imaging was performed on phantom solutions including pure ammonia, bovine serum albumin (BSA), and tissue homogenate samples doped with various ammonia concentrations. All CEST data were assessed by magnetization transfer ratio asymmetry. In addition, optical methods were used to determine possible structural changes of the proteins in the BSA phantom. In vivo feasibility measurements were acquired in one healthy participant and two patients suffering from HE, a disease associated with increased brain ammonia levels. The CEST effect of pure ammonia showed a base-catalyzed behavior. At pH values greater than 5.6 no CEST effect was observed. The APT-weighted signal was significantly reduced for ammonia concentrations of 5mM or more at fixed pH values within the different protein phantom solutions. The optical methods revealed no protein aggregation or denaturation for ammonia concentrations less than 5mM. The in vivo measurements showed tissue specific and global reduction of the observed CEST signal in patients with HE, possibly linked to pathologically increased ammonia levels. APT-weighted CEST imaging is sensitive to changes in ammonia concentrations. Thus, it seems useful for the investigation of pathologies with altered tissue ammonia concentrations such as HE. However, the underlying mechanism needs to be explored in more detail in future in vitro and in vivo investigations.

Live-cell single-molecule dynamics of PcG proteins imposed by the DIPG H3.3K27M mutation.

Over 80% of diffuse intrinsic pontine gliomas (DIPGs) harbor a point mutation in histone H3.3 where lysine 27 is substituted with methionine (H3.3K27M); however, how the mutation affects kinetics and function of PcG proteins remains elusive. We demonstrate that H3.3K27M prolongs the residence time and search time of Ezh2, but has no effect on its fraction bound to chromatin. In contrast, H3.3K27M has no effect on the residence time of Cbx7, but prolongs its search time and decreases its fraction bound to chromatin. We show that increasing expression of Cbx7 inhibits the proliferation of DIPG cells and prolongs its residence time. Our results highlight that the residence time of PcG proteins directly correlates with their functions and the search time of PcG proteins is critical for regulating their genomic occupancy. Together, our data provide mechanisms in which the cancer-causing histone mutation alters the binding and search dynamics of epigenetic complexes.

Good clinical and MRI outcome after arthroscopic autologous chondrocyte implantation for cartilage repair in the knee.

PURPOSE: To analyze the clinical outcome and cartilage regeneration after all-arthroscopic Autologous Chondrocyte Implantation (ACI) using chondrospheres® (ACT3D) for the treatment of full-size articular cartilage lesions at the knee. METHODS: Thirty consecutive patients treated by all-arthroscopic ACI for full-size articular cartilage lesions in an otherwise healthy knee were enrolled. The defects were located on the femoral condyles (n = 18), in the trochlea (n = 7) and at the patella (n = 5). Follow-up consisted of a clinical evaluation with assessment of subjective scores. Patient satisfaction was evaluated on a visual analog scale (VAS). 3-Tesla MRI and T2 mapping of the operated and the contralateral healthy knees were included to control the quality of the regenerated cartilage. The MOCART score was assessed by three blinded independent radiologists. RESULTS: At the mean follow-up of 3 years ± 10.2 months 26 of the 30 patients (86.6%) were subjectively highly satisfied with the surgical result and assured they would undergo the same procedure again. The mean Lysholm score increased to 77.7 ± 14.6, the mean subjective IKDC significantly to 84.2 ± 5.6 (p < 0.05) and all five subgroups of the KOOS improved significantly (p < 0.05). The subjective outcome was not influenced by the duration of symptoms, age, location, size of defects nor dose of spheroids. The modified MOCART score was a mean of 60 ± 21 (0-80) points. Twenty-four patients (82.7%) were rated higher than 60 points. T2 mapping documented similar cartilage quality of the area of the ACI and the same location at the contralateral knee. Three patients had a MOCART score of 0 with few or no cartilage regeneration on MRI and were considered as failure of the ACI. CONCLUSION: In this small cohort of 30 patients, minimal invasive all-arthroscopic ACT 3D using spheroids led to convincing clinical short-to-mid-term results with a significant increase in patients quality of life, satisfaction, reduction of pain, and improvement in knee function. The high morphologic integrity and quality of the ACI was reconfirmed by the Mocart Score and T2 mapping. LEVEL OF EVIDENCE: IV.

SASHA versus ShMOLLI: a comparison of T1 mapping methods in health and dilated cardiomyopathy at 3 T.

Cardiac Magnetic Resonance derived T1 mapping parameters are a non-invasive method of estimating diffuse myocardial fibrosis. This study aims to to determine the native T1 time, post contrast T1 time and extracellular volume (ECV) derived from T1 mapping and to evaluate the ability of T1 mapping techniques to discriminate healthy myocardium from dilated cardiomyopathy. Seventy-nine participants underwent cardiac magnetic resonance imaging at the Baker Heart and Diabetes Institute, Melbourne, Australia. Fifty-seven healthy volunteers and twenty-two patients with Dilated cardiomyopathy were included in the study. Each participant had T1 mapping sequences performed at 3 T in the mid short axis slice-both SASHA and ShMOLLI T1 mapping were performed. Native T1, post contrast T1 and ECV values were compared in health and dilated cardiomyopathy. Native T1, post contrast T1 and ECV differed significantly between SASHA and ShMOLLI techniques (P < 0.001). All T1 parameters had similar ability to discriminate normal from abnormal myocardium (ROC AUC 0.691 to 0.830). Converting T1 values to Z scores significantly improved the agreement between SASHA and ShMOLLI techniques, particularly for post contrast T1 (ICC 0.19 to 0.895) and ECV (ICC 0.461 to 0.880). T1 mapping values from SASHA and ShMOLLI show strong correlation for post contrast measures, though with a consistent offset for all measures in health and dilated cardiomyopathy. All measures obtained using SASHA and ShMOLLI allow good discrimination between dilated cardiomyopathy and normal myocardium.

Evaluating the cartilage adjacent to the site of repair surgery with glycosaminoglycan-specific magnetic resonance imaging.

PURPOSE: The glycosaminoglycan (GAG) chemical exchange saturation transfer (CEST) imaging method (gagCEST) makes it possible to assess and quantify the GAG concentration in human cartilage. This biochemical imaging technique facilitates detection of the loss of GAG in the course of osteoarthritis. The gagCEST technique was used to analyse the perilesional zone (PLZ) adjacent to repair tissue after cartilage repair surgery, to determine whether there are biochemical changes present in the sense of degeneration. METHOD: Asymmetries in the PLZ of cartilage defects in 11 patients, who had been treated by microfracturing or matrix-associated autologous chondrocyte transplantation (MACT), were measured by gagCEST on a 7-T whole-body system. These results were correlated with gagCEST asymmetries of healthy reference cartilage (RC), measured anterior and posterior to the PLZ and to the repair tissue (RT). RESULTS: The mean gagCEST asymmetry for the anterior PLZ was 4.8% (±4.4), for the posterior PLZ 5.4% (±2.3), for the anterior RC 6.6% (±3.5) and 7.2% (±3.3) for the posterior RC and 4.5% (±2.3) for the RT. The difference between the anterior PLZ and the anterior RC (p = 0.019), the posterior PLZ and the posterior RC (p = 0.005), and the mean RC and the RT (p = 0.021) were all statistically significant. The measurements between RT and mean PLZ did not reveal significant results (p = 0.398). CONCLUSIONS: The gagCEST method provides a potentially useful biomarker for the loss of GAGs, indicating cartilage degeneration in the PLZ. Pre-operative and post-operative monitoring of the biomechanical state of the cartilage might influence intra-operative decision-making concerning the extent of cartilage resection or might give information of the success of the treatment post-operatively.

Comparison of Routine Knee Magnetic Resonance Imaging at 3 T and 7 T.

OBJECTIVE: The aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR] and diagnostic confidence) from a standard knee magnetic resonance imaging (MRI) examination with comparable sequence protocols and acquisition times at 3 T and at 7 T. MATERIALS AND METHODS: Forty patients experiencing knee pain of unknown etiology underwent comparable MR protocols with standard turbo-spin echo and short tau inversion recovery sequences of the knee joint (5 sequences) at 3 T and 7 T. For quantitative analysis, SNR was determined using these 5 sequences and 3 additional morphological sequences. For a semiquantitative assessment of diagnostic confidence, a diagnostic confidence score (DCS) was assigned, using a 10-point scale. Two experienced radiologists who specialized in musculoskeletal imaging and who were blinded to the field-strength independently assessed 22 potential pathological findings, in total, in 4 anatomically defined areas in the knee joint and rated their diagnostic confidence. RESULTS: In quantitative analysis, all sequences provided higher voxel-volume-adjusted SNR values at 7 T compared with that at 3 T. In semiquantitative analysis, summed DCS values for potential pathological findings in each of the 4 anatomically defined areas were higher at 7 T compared with that at 3 T. There was a statistically significant improvement in the DCS for both readers at 7 T for the diagnosis and exclusion of focal or diffuse grade I or II cartilage defects in the patellar cartilage. For 8 potential pathological findings, a statistically significant difference between the 2 field-strengths could be observed for 1 reader only. For the residual 13 potential pathological findings, there was no statistically significant difference observed. The percentage of concordant ratings was 84.6% at 3 T and 85.4% at 7 T. CONCLUSIONS: Ultra-high-field MRI at 7 T improved the overall diagnostic confidence in routine MRI of the knee joint compared with that at 3 T. This is especially true for small joint structures and subtle lesions. Higher spatial resolution was identified as the main reason for this improvement.

Noninvasive amide proton transfer magnetic resonance imaging in evaluating the grading and cellularity of gliomas.

Using noninvasive magnetic resonance imaging techniques to accurately evaluate the grading and cellularity of gliomas is beneficial for improving the patient outcomes. Amide proton transfer imaging is a noninvasive molecular magnetic resonance imaging technique based on chemical exchange saturation transfer mechanism that detects endogenous mobile proteins and peptides in biological tissues. Between August 2012 and November 2015, a total number of 44 patients with pathologically proven gliomas were included in this study. We compared the capability of amide proton transfer magnetic resonance imaging with that of noninvasive diffusion-weighted imaging and noninvasive 3-dimensional pseudo-continuous arterial spin imaging in evaluating the grading and cellularity of gliomas. Our results reveal that amide proton transfer magnetic resonance imaging is a superior imaging technique to diffusion-weighted imaging and 3-dimensional pseudo-continuous arterial spin imaging in the grading of gliomas. In addition, our results showed that the Ki-67 index correlated better with the amide proton transfer-weighted signal intensity than with the apparent diffusion coefficient value or the cerebral blood flow value in the gliomas. Amide proton transfer magnetic resonance imaging is a promising method for predicting the grading and cellularity of gliomas.

Higher resolution cine imaging with compressed sensing for accelerated clinical left ventricular evaluation.

PURPOSE: To assess the clinical feasibility of a compressed sensing cine magnetic resonance imaging (MRI) sequence of both high temporal and spatial resolution (CS_bSSFP) in comparison to a balanced steady-state free precession cine (bSSFP) sequence for reliable quantification of left ventricular (LV) volumes and mass. MATERIALS AND METHODS: Segmented MRI cine images were acquired on a 1.5T scanner in 50 patients in the LV short-axis stack orientation using a retrospectively gated conventional bSSFP sequence (generalized autocalibrating partially parallel acquisition [GRAPPA] acceleration factor 2), followed by a prospectively triggered CS_bSSFP sequence with net acceleration factor of 8. Image quality was assessed by published criteria. Comparison of sequences was made in LV volumes and mass, image quality score, quantitative regional myocardial wall motion, and imaging time using Pearson's correlation, Bland-Altman and paired 2-tailed Student's t-test. RESULTS: Differences (bSSFP minus CS_bSSFP, mean ± SD) and Pearson's correlations were 14.8 ± 16.3 (P = 0.31) and r = 0.98 (P < 0.0001) for end-diastolic volume (EDV), 8.4 ± 11.3 (P = 0.54) and r = 0.99 (P < 0.0001) for end-systolic volume (ESV), -0.4 ± 2.5 (P = 0.87) and r = 0.97 (P < 0.0001) for EF, and -0.9 ± 11.8 (P = 0.92) and r = 0.97 (P < 0.0001) for LV mass. Bland-Altman analyses [bias and (limits of agreement)] revealed strong agreement in LVEDV [8.7 ml, (-12.1, 29.6)], LVESV [4.3 ml, (-11.9, 20.6)], LVEF [-0.02%, (-5.37, 5.33)], and myocardial mass [-6.1 g, (-14.7, 26.9)]. Image quality was comparable with a similar mean score (P = 0.42), with a good correlation in image quality observed (r = 0.68, P < 0.0001). Quantitative regional myocardial wall motion demonstrated strong correlation between the sequences (r = 0.87, P < 0.0001). Imaging time was significantly shorter for the CS_bSSFP sequence (1.1 ± 0.5 versus 5.6 ± 1.6 min, P < 0.0001). CONCLUSION: The novel high-resolution cine CS_bSSFP accurately and reliably quantitates LV volumes and mass, shortens acquisition times, and is clinically feasible. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1693-1699.

An MRspec database query and visualization engine with applications as a clinical diagnostic and research tool.

PURPOSE: Proton magnetic resonance spectroscopy (MRspec), one of the very few techniques for in vivo assessment of neuro-metabolic profiles, is often complicated by lack of standard population norms and paucity of computational tools. METHODS: 7035 scans and clinical information from 4430 pediatric patients were collected from 2008 to 2014. Scans were conducted using a 1.5T (n=3664) or 3T scanner (n=3371), and with either a long (144ms, n=5559) or short echo time (35ms, n=1476). 3055 of these scans were localized in the basal ganglia (BG), 1211 in parieto-occipital white matter (WM). 34 metabolites were quantified using LCModel. A web application using MySQL, Python and Flask was developed to facilitate the exploration of the data set. RESULTS: Already piloting the application revealed numerous insights. (1), N-acetylaspartate (NAA) increased throughout all ages. During early infancy, total choline was highly varied and myo-inositol demonstrated a downward trend. (2), Total creatine (tCr) and creatine increased throughout childhood and adolescence, though phosphocreatine (PCr) remained constant beyond 200days. (3), tCr was higher in BG than WM. (4), No obvious gender-related differences were observed. (5), Field strength affects quantification using LCModel for some metabolites, most prominently for tCr and total NAA. (6), Outlier analysis identified patients treated with vigabatrin through elevated γ-aminobutyrate, and patients with Klippel-Feil syndrome, Leigh disease and L2-hydroxyglutaric aciduria through low choline in BG. CONCLUSIONS: We have established the largest MRSpec database and developed a robust and flexible computational tool for facilitating the exploration of vast metabolite datasets that proved its value for discovering neurochemical trends for clinical diagnosis, treatment monitoring, and research. Open access will lead to its widespread use, improving the diagnostic yield and contributing to better understanding of metabolic processes and conditions in the brain.

[Chemical Exchange Saturation Transfer Imaging of Creatine Metabolites: a 3.0 T MRI Pilot].

OBJECTIVE: To determine the feasibility of using chemical exchange saturation transfer (CEST) imaging to measure creatine (Cr) metabolites with 3.0 T MR. METHODS: Phantoms containing different concentrations of Cr under various pH conditions were studied with CEST sequence on 3.0 T MR imaging. CEST effect and Z spectra were analyzed. RESULTS: Cr exhibited significant CEST effect (± 1.8 ppm, F = 99.08, P < 0.001) on 3.0 T MR imaging, and positive correlation was found between the signal intensity and concentration of Cr (r = 0.963, P < 0.001). The CEST effect showed pH dependency of Cr (r = 0.41, P = 0.035). CONCLUSION: Creatine CEST imaging can be performed on 3.0 T MR imaging. Creatine concentrations and pH influence CEST effect.

Improvement of water saturation shift referencing by sequence and analysis optimization to enhance chemical exchange saturation transfer imaging.

PURPOSE: To optimize B0-field inhomogeneity correction for chemical exchange saturation transfer (CEST) imaging by investigating different water saturation shift referencing (WASSR) Z-spectrum shapes and different frequency correction techniques. METHODS: WASSR Z-spectra were simulated for different B1-fields and pulse durations (PD). Two parameter settings were used for further simulations and experiments (WASSR1: B1=0.1 µT, PD=50ms; WASSR2: B1=0.3 µT, PD=40ms). Four frequency correction techniques were investigated: 1) MinW: Minimum of the spline-interpolated WASSR-spectrum; 2) MSCF: maximum symmetry center frequency algorithm; 3) PMSCF: further development of MSCF algorithm; 4) BFit: fit with Bloch equations. Performance of frequency correction was assessed with Monte-Carlo simulations and in-vivo MR examinations in the brain and intervertebral disks. RESULTS: Different shapes of WASSR-Z-spectra were obtained by changing B1 and PD including spectra with one (1-Peak) or two (2-Peak) minima. WASSR1 resulted in 1-Peak WASSR-spectrum, whereas WASSR2 resulted in 2-Peak WASSR-spectrum. Both Monte-Carlo simulations and in-vivo MR examinations revealed highest accuracy of field-inhomogeneity correction with WASSR1 combined with PMSCF or BFit. CONCLUSION: Using a WASSR sequence, which results in a Z-spectrum with a single absorption peak, in combination with advanced postprocessing algorithms enables improved B0-field inhomogeneity correction for CEST imaging.

Reproducibility and regional variations of an improved gagCEST protocol for the in vivo evaluation of knee cartilage at 7 T.

OBJECTIVE: The objective was to establish a gagCEST protocol that would enable robust and reproducible assessment of the glycosaminoglycan (GAG) content in knee cartilage at 7 T within a clinically feasible measurement time. MATERIALS AND METHODS: Ten young healthy volunteers (mean age 26 years, range 24-28, five males, five females) were examined on a 7 T MR system. Informed consent was obtained from all individual participants prior to enrollment into the study. Each volunteer was measured twice for reproducibility assessment. The examined knee was immobilized using a custom-made fixation device. For the gagCEST measurement, a prototype segmented 3-D RF-spoiled gradient-echo sequence with an improved saturation scheme employing adiabatic pulses was used in a scan time of 19 min. The asymmetry of the Z-spectra (MTRasym) in selected regions of interest in knee cartilage was calculated. Differences in MTRasym between different regions were evaluated using ANOVA and the Bonferroni corrected post hoc test. RESULTS: The improvement of the saturation scheme reduced the influence of field inhomogeneities, resulted in more uniform saturation, and allowed for good reproducibility in a reasonable measurement time (19 min), as demonstrated by an intraclass correlation coefficient of 0.77. Improved fixation helped to reduce motion artifacts. Whereas similar MTRasym values were found for weight-bearing and non-weight-bearing femoral cartilage, lower values were observed in the trochlear groove (p = 0.028), patellar (p = 0.015) and tibial cartilage (p < 0.001) when compared to non-weight-bearing femoral cartilage. CONCLUSION: Reasonable reproducibility and sensitivity to regional differences in GAG content suggests that the improved gagCEST protocol might be useful for assessing the biochemical changes in articular cartilage that are associated with early stages of cartilage degeneration.