Metal-Free-Catalyzed Three-Component [2+2+2] Annulation Reaction of [60]Fullerene, Ketones, and Indoles: Access to Diverse [60]Fullerene-Fused 1,2-Tetrahydrocarbazoles.

The first example of metal-free-catalyzed multicomponent annulation reaction of [60]fullerene has been developed for concise and efficient construction of novel [60]fullerene-fused 1,2-tetrahydrocarbazoles. Using inexpensive and readily available I2 as a catalyst, [60]fullerene, ketones, and indoles undergo a formal [2+2+2] annulation process to conveniently assemble diverse 1,2-tetrahydrocarbazoles. Mechanistic studies indicate that this reaction proceeds through I2-promoted generation of a 3-vinylindole structure with the characteristics of a conjugated diene followed by cycloaddition to [60]fullerene.

Chemical Exchange Saturation Transfer MRI Signal Loss of the Substantia Nigra as an Imaging Biomarker to Evaluate the Diagnosis and Severity of Parkinson's Disease.

The early diagnosis of Parkinson's disease (PD) and the accurate evaluation of disease severity are crucial for intervention and treatment in PD patients. In this study, we applied chemical exchange saturation transfer (CEST) imaging to patients at different stages of PD and explored the clinical value of the CEST signal loss of the substantia nigra as an imaging biomarker of PD. The measured CEST signal intensities (including amide proton transfer-weighted or APTw, and total CEST or CESTtotal) of the substantia nigra in PD patients showed a significantly decreased tendency with PD progression. Compared to normal controls, the APTw and CEST total intensities of PD patients significantly decreased at both the early and advanced or late stages. These APTw and CESTtotal values of the substantia nigra were also significantly lower in advanced or late stage PD patients than in early stage PD patients. For PD patients with unilateral symptoms, the APTw and CESTtotal values in the substantia nigra on the affected side were significantly lower than those in normal controls. Both the APTw and CESTtotal values of PD were significantly correlated with the severity of disease and disease duration. Our findings suggest that the CEST MRI signal of the substantia nigra is a potential imaging biomarker for the diagnosis and monitoring of the severity of PD.

In Situ Generated TEMPO Oxoammonium Salt Mediated Tandem Cyclization of ß-Oxoamides with Amine Hydrochlorides for the Synthesis of Pyrrolin-4-ones.

A novel in situ generated TEMPO oxoammonium salt mediated one-pot tandem reaction has been developed for the straightforward construction of pyrrolin-4-ones from readily available ß-oxoamides with amine hydrochlorides. The reaction tolerates various functional groups and represents a reliable method for the synthesis of highly substituted pyrrolin-4-ones in good yields under mild conditions. Detailed mechanistic studies disclosed that TEMPO oxoammonium salt generated in situ was crucial for the transformation involving the formation of enaminone precursors in situ by condensation of the ß-oxoamides with amines, followed by sequential oxidative coupling with ß-oxoamides, intramolecular cyclization, and 1,2-alkyl migration steps.

Evolution of Cerebral Ischemia Assessed by Amide Proton Transfer-Weighted MRI.

Amide proton transfer-weighted (APTW) magnetic resonance imaging (MRI) has recently become a potentially important tool for evaluating acidosis in ischemic stroke. The purpose of this study was to evaluate the dynamic pH-related changes in the lesions in patients with ischemia. Thirty-nine patients with ischemic stroke (symptom onset to imaging time ranging 2 h-7 days) were examined with a 3.0-T MRI system. Patients were divided into four groups: at the hyperacute stage (onset time ≤ 6 h), at the acute stage (6 h < onset time ≤ 48 h), at the early subacute stage (48 h < onset time ≤ 96 h), and at the late subacute stage (96 h < onset time ≤ 168 h). The APTW signal intensities were quantitatively measured in multiple ischemic regions for each patient. Compared with the contralateral normal white matter, APTW signals were significantly lower in ischemic tissue for all four stages (P < 0.05). The APTW signal intensities (APTWave and APTWmin) increased consistently with onset time (R2 = 0.11, P = 0.040; R2 = 0.13, P = 0.022, respectively). APTWmax-min showed a continued reduction with onset time (R2 = 0.44, P < 0.001). Our results suggest that persistent tissue acidification could occur after ischemia, and as the time from stroke onset increases, the acidotic environment would alleviate. APTW signal intensities could reflect pH-weighted properties in ischemic tissue at different stages and time points.

Quantitative assessment of the effects of water proton concentration and water T1 changes on amide proton transfer (APT) and nuclear overhauser enhancement (NOE) MRI: The origin of the APT imaging signal in brain tumor.

PURPOSE: To quantify pure chemical exchange-dependent saturation transfer (CEST) related amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) signals in a rat glioma model and to investigate the mixed effects of water content and water T1 on APT and NOE imaging signals. METHODS: Eleven U87 tumor-bearing rats were scanned at 4.7 T. A relatively accurate mathematical approach, based on extrapolated semisolid magnetization-transfer reference signals, was used to remove the concurrent effects of direct water saturation and semisolid magnetization-transfer. Pure APT and NOE signals, in addition to the commonly used magnetization-transfer-ratio asymmetry at 3.5 ppm, MTRasym (3.5ppm), were assessed. RESULTS: The measured APT signal intensity of the tumor (11.06%, much larger than the value reported in the literature) was the major contributor (approximately 80.6%) to the MTRasym (3.5ppm) contrast between the tumor and the contralateral brain region. Both the water content ([water proton]) and water T1 (T1w ) were increased in the tumor, but there were no significant correlations among APT, NOE, or MTRasym (3.5ppm) signals and T1w /[water proton]. CONCLUSION: The effect of increasing T1w on the CEST signal in the tumor was mostly eliminated by the effect of increasing water content, and the observed APT-weighted hyperintensity in the tumor should be dominated by the increased amide proton concentration. Magn Reson Med 77:855-863, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Accelerating chemical exchange saturation transfer (CEST) MRI by combining compressed sensing and sensitivity encoding techniques.

PURPOSE: To evaluate the feasibility of accelerated chemical-exchange-saturation-transfer (CEST) imaging using a combination of compressed sensing (CS) and sensitivity encoding (SENSE) at 3 Tesla. THEORY AND METHODS: Two healthy volunteers and six high-grade glioma patients were recruited. Raw CEST image k-space data were acquired (with varied radiofrequency saturation power levels for the healthy volunteer study), and a sequential CS and SENSE reconstruction (CS-SENSE) was assessed. The MTRasym (3.5 ppm) signals were compared with varied CS-SENSE acceleration factors. RESULTS: In the healthy volunteer study, a CS-SENSE acceleration factor of R = 2 × 2 (CS × SENSE) was achieved without compromising the reconstructed MTRasym (3.5 ppm) image quality. The MTRasym (3.5 ppm) signals obtained from the CS-SENSE reconstruction with R = 2 × 2 were well preserved compared with the reference image (R = 2 for only SENSE). In the glioma patient study, the MTRasym (3.5 ppm) signals were significantly higher in the tumor region (Gd-enhancing tumor core) than in the normal-appearing white matter (P < 0.001). There was no significant MTRasym (3.5 ppm) difference between the reference image and CS-SENSE-reconstructed image in the acceleration factor of R = 2 × 2. CONCLUSION: Combining the SENSE technique with CS (R = 2 × 2) enables considerable acceleration of CEST image acquisition and potentially has a wide range of clinical applications. Magn Reson Med 77:779-786, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Chemical exchange saturation transfer (CEST) imaging with fast variably-accelerated sensitivity encoding (vSENSE).

PURPOSE: The widespread clinical use of chemical exchange saturation transfer (CEST) imaging is hampered by relatively long scan times due to its requirement that multiple saturation-offset image frames be acquired. Here, a novel variably-accelerated sensitivity encoding (vSENSE) method is proposed that provides faster CEST acquisition than conventional SENSE. THEORY AND METHODS: The vSENSE method fully samples one CEST saturation frame, then undersamples the other frames variably. The fully-sampled frame, in conjunction with newly proposed incoherence absorption and artifact suppression strategies, improves the accuracy of sensitivity maps and permits higher acceleration factors for the other undersampled frames than regular SENSE. vSENSE is validated in a phantom, a normal volunteer and eight brain tumor patients at 3 Tesla. RESULTS: vSENSE with an acceleration factor of four generated a 3-6 times smaller error on average than conventional SENSE (P ≤ 0.02), with acceleration factors of 2-4, as compared with full k-space reconstruction. vSENSE permitted four-fold acceleration for amide proton transfer-weighted images, while regular SENSE could only provide a factor of two. When conventional SENSE is used with vSENSE's variable undersampling pattern, erroneous (∼9%) z-spectra result. CONCLUSION: The vSENSE method enabled twice the acceleration and generated more accurate images than conventional SENSE. Magn Reson Med 77:2225-2238, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Insight into the quantitative metrics of chemical exchange saturation transfer (CEST) imaging.

PURPOSE: To evaluate the reliability of four CEST imaging metrics for brain tumors, at varied saturation power levels and magnetic field strengths (3-9.4 Tesla (T)). METHODS: A five-pool proton exchange model (free water, semisolid, amide, amine, and NOE-related protons) was used for the simulations. For the in vivo study, eight glioma-bearing rats were scanned at 4.7 T. The CEST ratio (CESTR), CESTR normalized with the reference value (CESTRnr ), inverse Z-spectrum-based (MTRRex ), and apparent exchange-related relaxation (AREX) were compared. RESULTS: The simulated CEST signal intensities using MTRRex and AREX were substantially increased at relatively high radiofrequency (RF) saturation powers at 3 T and 4.7 T, whereas CESTR and CESTRnr metrics remained relatively stable. There were tremendously high MTRRex and AREX signals around the water frequency at all field strengths because of the small denominators. In the rat tumor study at 4.7 T, both CESTR and CESTRnr showed clear contrasts in the tumor with respect to the normal tissue across all saturation power levels (0.5-3 µT), whereas the AREX showed negligible to negative insignificant contrasts. CONCLUSIONS: CEST metrics must be carefully selected based on the different experimental settings. CESTR and CESTRnr are more reliable at 3 T (a clinical field strength) and 4.7 T. Magn Reson Med 77:1853-1865, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Perturbation of longitudinal relaxation rate in rotating frame (PLRF) analysis for quantification of chemical exchange saturation transfer signal in a transient state.

PURPOSE: To develop a novel analytical method for quantification of chemical exchange saturation transfer (CEST) in the transient state. The proposed method aims to reduce the effects of non-chemical-exchange (non-CE) parameters on the CEST signal, emphasizing the effect of chemical exchange. METHODS: The difference in the longitudinal relaxation rate in the rotating frame ( ΔR1ρ) was calculated based on perturbation of the Z-value by R1ρ, and a saturation-pulse-amplitude-compensated exchange-dependent relaxation rate (SPACER) was determined with a high-exchange-rate approximation. In both phantom and human subject experiments, MTRasym (representative of the traditional CEST index), ΔR1ρ, and SPACER were measured, evaluated, and compared by altering the non-CE parameters in a transient-state continuous-wave CEST sequence. RESULTS: In line with the theoretical expectation, our experimental data demonstrate that the effects of the non-CE parameters can be more effectively reduced using the proposed indices (  ΔR1ρ and SPACER) than using the traditional CEST index ( MTRasym). CONCLUSION: The proposed method allows for the chemical exchange weight to be better emphasized in the transient-state CEST signal, which is beneficial, in practice, for quantifying the CEST signal. Magn Reson Med 78:1711-1723, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Magnetization Transfer and Amide Proton Transfer MRI of Neonatal Brain Development.

Purpose. This study aims to evaluate the process of brain development in neonates using combined amide proton transfer (APT) imaging and conventional magnetization transfer (MT) imaging. Materials and Methods. Case data were reviewed for all patients hospitalized in our institution's neonatal ward. Patients underwent APT and MT imaging (a single protocol) immediately following the routine MR examination. Single-slice APT/MT axial imaging was performed at the level of the basal ganglia. APT and MT ratio (MTR) measurements were performed in multiple brain regions of interest (ROIs). Data was statistically analyzed in order to assess for significant differences between the different regions of the brain or correlation with patient gestational age. Results. A total of 38 neonates were included in the study, with ages ranging from 27 to 41 weeks' corrected gestational age. There were statistically significant differences in both APT and MTR measurements between the frontal lobes, basal ganglia, and occipital lobes (APT: frontal lobe versus occipital lobe P = 0.031 and other groups P = 0.00; MTR: frontal lobe versus occipital lobe P = 0.034 and other groups P = 0.00). Furthermore, APT and MTR in above brain regions exhibited positive linear correlations with patient gestational age. Conclusions. APT/MT imaging can provide valuable information about the process of the neonatal brain development at the molecular level.

Assessment of Glioma Response to Radiotherapy Using Multiple MRI Biomarkers with Manual and Semiautomated Segmentation Algorithms.

BACKGROUND AND PURPOSE: Multimodality magnetic resonance imaging (MRI) can provide complementary information in the assessment of brain tumors. We aimed to segment tumor in amide proton transfer-weighted (APTw) images and to investigate multiparametric MRI biomarkers for the assessment of glioma response to radiotherapy. For tumor extraction, we evaluated a semiautomated segmentation method based on region of interest (ROI) results by comparing it with the manual segmentation method. METHODS: Thirteen nude rats injected with U87 tumor cells were irradiated by an 8-Gy radiation dose. All MRI scans were performed on a 4.7-T animal scanner preradiation, and at day 1, day 4, and day 8 postradiation. Two experts performed manual and semiautomated methods to extract tumor ROIs on APTw images. Multimodality MRI signals of the tumors, including structural (T2 and T1 ), functional (apparent diffusion coefficient and blood flow), and molecular (APTw and magnetization transfer ratio or MTR), were calculated and compared quantitatively. RESULTS: The semiautomated method provided more reliable tumor extraction results on APTw images than the manual segmentation, in less time. A considerable increase in the ADC intensities of the tumor was observed during the postradiation. A steady decrease in the blood flow values and in the APTw signal intensities were found after radiotherapy. CONCLUSIONS: The semiautomated method of tumor extraction showed greater efficiency and stability than the manual method. Apparent diffusion coefficient, blood flow, and APTw are all useful biomarkers in assessing glioma response to radiotherapy.

Accuracy of PET/MR image coregistration of cervical lesions.

PURPOSE: This study aimed to evaluate the accuracy of sequential whole-body PET/MR image coregistration of cervical lesions. MATERIALS AND METHODS: Twenty-five patients with cervical carcinomas underwent fluorine-18 fluorodeoxyglucose PET/MR before radiotherapy. MR-volumes of interest (VOIs), PET-VOIs, and apparent diffusion coefficient (ADC)-VOIs were outlined manually on T2-weighted MR images, PET images, and ADC maps. The difference between the lesion centers on PET and MR was determined by calculating the distance of the respective geometric center of gravity. In addition, the tumor volume contour differences were assessed using the dice similarity coefficient for PET and ADC. Results were analyzed by mean±SD and a two-sample t-test. RESULTS: The mean values of the center of gravity mismatch were relatively higher with lesions between PET and ADC (5.79±1.70 mm) than that between PET and MR-T2 (5.22±1.97 mm; P=0.304). Tumor location overlap difference between MR-T2 and PET images (0.64±0.13) was larger than that between ADC and PET (0.56±0.14; P=0.054). The average differences between the centers of lesions on PET and T2-weighted images were 6.25±1.91, 5.24±2.17, and 4.30±1.30 mm for MR-VOI less than 14, 14-62, and at least 62 ml. The average differences between the center of lesions on PET and ADC were 5.97±1.48, 5.43±1.40, and 5.78±2.75 mm, respectively. Image registration tended to be slightly less accurate in the smaller lesions than in the larger lesions (P>0.05). The average overlaps were 0.51±0.13, 0.63±0.10, and 0.76±0.03 between the T2-weighted image and PET, respectively. The average overlaps were 0.44±0.14, 0.58±0.11, and 0.66±0.04 between the ADC and PET, respectively. Larger tumors had a higher degree of overlap compared with small tumors (P<0.05). CONCLUSION: Image coregistration of cervical lesions is usually accurate in sequential whole-body PET/MR. The accuracy of image registration between MR-T2 and PET was larger than that between ADC and PET. Image registration tended to be more accurate in the larger lesions.

Amide Proton Transfer (APT) MR imaging and Magnetization Transfer (MT) MR imaging of pediatric brain development.

OBJECTIVES: To quantify the brain maturation process during childhood using combined amide proton transfer (APT) and conventional magnetization transfer (MT) imaging at 3 Tesla. METHODS: Eighty-two neurodevelopmentally normal children (44 males and 38 females; age range, 2-190 months) were imaged using an APT/MT imaging protocol with multiple saturation frequency offsets. The APT-weighted (APTW) and MT ratio (MTR) signals were quantitatively analyzed in multiple brain areas. Age-related changes in MTR and APTW were evaluated with a non-linear regression analysis. RESULTS: The APTW signals followed a decreasing exponential curve with age in all brain regions measured (R(2) = 0.7-0.8 for the corpus callosum, frontal and occipital white matter, and centrum semiovale). The most significant changes appeared within the first year. At maturation, larger decreases in APTW and lower APTW values were found in the white matter. On the contrary, the MTR signals followed an increasing exponential curve with age in the same brain regions measured, with the most significant changes appearing within the initial 2 years. There was an inverse correlation between the MTR and APTW signal intensities during brain maturation. CONCLUSIONS: Together with MT imaging, protein-based APT imaging can provide additional information in assessing brain myelination in the paediatric population. KEY POINTS: • APTW signals followed a decreasing exponential curve with age. • The most significant APTW changes appeared within the first year • At maturation, larger APTW decreases and lower APTW appeared in white matter • MTR signals followed an increasing exponential curve with age.

Highly-accelerated CEST Measurements in Three Dimensions with Linear Algebraic Modeling.

CEST MRI can provide valuable molecular level information in vivo, but its translation to routine clinics is hindered by long imaging times. Regional average CEST measurements often suffice for quantitative evaluation, diagnosis, and treatment assessment, while allowing much shorter scan times. Recently, the spectroscopy with linear algebraic modeling (SLAM) method was adapted for CEST MRI in two dimensions (2D), directly obtaining compartmental-average measurements manifold faster than conventional CEST. Here, the SLAM CEST method is extended from 2D to 3D, and applied to patients with brain tumors with acceleration factors of up to 98-fold.

3D interslab echo-shifted FLASH sequence for susceptibility weighted imaging.

PURPOSE: To develop a novel three-dimensional (3D) sequence for susceptibility weighted imaging that is able to reduce scan time substantially while maintaining high image signal-to-noise ratio (SNR). METHODS: The proposed fast T2 *-weighted sequence was based on a 3D full-balanced gradient frame and a pair of crusher gradients. The pair of crusher gradients were used to shift MR signal from the repetition time where the MR signal was originated to a later repetition time to enhance T2 * weighting. To avoid image SNR reduction due to the repeated signal excitations by later RF pulses, as it would occur for typical echo-shifted (ES) FLASH, an interslab scan mode for the fast T2 *-weighted sequence was introduced for signal acquisition. The effectiveness of this novel sequence was evaluated by comparing it with 3D FLASH and ES-FLASH sequences. RESULTS: The proposed interslab ES T2 *-weighted sequence was able to reduce the scan time by half with a SNR comparable to the typical multislab FLASH. Besides, it yielded a higher image SNR than the traditional multislab ES-FLASH and was more flexible than the whole-volume ES-FLASH. CONCLUSION: An interslab ES sequence was developed with high time efficiency and relatively high image SNR compared with the conventional acquisition sequences. Magn Reson Med 76:222-228, 2016. © 2015 Wiley Periodicals, Inc.

Selecting the reference image for registration of CEST series.

BACKGROUND: To compare different reference images selected for registration among chemical exchange saturation transfer (CEST) series. MATERIALS AND METHODS: Five normal volunteers and eight brain tumor patients were studied on a 3 Tesla scanner. Image registration was performed by choosing each of the acquired CEST saturation or unsaturation dynamic images as the reference. CEST images at 3.5 ppm (amide proton transfer, APT) were computed for each motion-corrected data set after main magnetic field inhomogeneity correction. A uniformity index was defined to quantify the efficacy of image registration using different reference images. Joint histograms and the structural similarity index (SSIM) were used to analyze the intrinsic image similarity between various dynamic images. RESULTS: Image registration increased the average uniformity index by 18% if the 3.5 ppm saturated image was selected as the reference image. However, registering to the unsaturated dynamic image reduced the uniformity index by 13% on average. The joint histogram analysis showed that the saturated dynamic images were highly similar (SSIM = 0.89 ± 0.01), and were considerably different from the unsaturated dynamic image (SSIM = 0.58 ± 0.03). CONCLUSION: The selection of the 3.5 ppm dynamic image as the reference image generated the highest uniformity index for APT imaging though other saturated images were equally suited as reference images.

DWI using navigated interleaved multishot EPI with realigned GRAPPA reconstruction.

PURPOSE: A novel k-space reconstruction method is proposed for generating diffusion-weighted imaging (DWI) using navigated interleaved multishot EPI (msEPI). THEORY AND METHODS: In interleaved msEPI, each shot of data acquired from one coil channel is a subset of the full k-space of that channel. All the k-space subsets of one channel can be treated as an undersampled dataset of a virtual multichannel data, which can be reconstructed by the GRAPPA algorithm after k-space realignment. The intershot phase variations are directly compensated using navigator echoes as the auto-calibrating data in GRAPPA reconstruction. In cases of multichannel msEPI data, all the virtual channels and actual channels can be integrated into a single GRAPPA reconstruction step. The proposed method is tested using both simulation and in-vivo data. The simulation results produced by the proposed method and a SENSE-based method are compared. RESULTS: The simulated images generated by the proposed method exhibit less relative error compared with those generated by the SENSE method. Inconsistent shot-to-shot phase variation is naturally resolved by GRAPPA calibration without additional phase map processing. High-quality brain DWI with submillimeter resolution is obtained using our proposed reconstruction method. CONCLUSION: A novel k-space msEPI reconstruction method has been developed for generating high-quality diffusion imaging.

Chemical Exchange Saturation Transfer MR Imaging is Superior to Diffusion-Tensor Imaging in the Diagnosis and Severity Evaluation of Parkinson's Disease: A Study on Substantia Nigra and Striatum.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal cell loss. To date, the diagnosis of PD is still based primarily on the clinical manifestations, which may be typical and obvious only in advanced-stage PD. Thus, it is crucial to find a reliable marker for the diagnosis of PD. We conducted this study to assess the diagnostic efficiency of chemical exchange saturation transfer (CEST) imaging and diffusion-tensor imaging (DTI) in PD at 3 T by evaluating changes on substantia nigra and striatum. Twenty-three PD patients and twenty-three age-matched normal controls were recruited. All patients and controls were imaged on a 3-T MR system, using an eight-channel head coil. CEST imaging was acquired in two transverse slices of the head, including substantia nigra and striatum. The magnetization transfer ratio asymmetry at 3.5 ppm, MTRasym(3.5 ppm), and the total CEST signal intensity between 0 and 4 ppm were calculated. Multi-slice DTI was acquired for all the patients and normal controls. Quantitative analysis was performed on the substantia nigra, globus pallidus, putamen, and caudate. The MTRasym(3.5 ppm) value, the total CEST signal intensity, and fractional anisotropy value of the substantia nigra were all significantly lower in PD patients than in normal controls (P = 0.003, P = 0.004, and P < 0.001, respectively). The MTRasym(3.5 ppm) values of the putamen and the caudate were significantly higher in PD patients than in normal controls (P = 0.010 and P = 0.009, respectively). There were no significant differences for the mean diffusivity in these four regions between PD patients and normal controls. In conclusion, CEST MR imaging provided multiple CEST image contrasts in the substantia nigra and the striatum in PD and may be superior to DTI in the diagnosis of PD.

A voxelation-corrected non-stationary 3D cluster-size test based on random field theory.

Cluster-size tests (CSTs) based on random field theory (RFT) are commonly adopted to identify significant differences in brain images. However, the use of RFT in CSTs rests on the assumption of uniform smoothness (stationarity). When images are non-stationary, CSTs based on RFT will likely lead to increased false positives in smooth regions and reduced power in rough regions. An adjustment to the cluster size according to the local smoothness at each voxel has been proposed for the standard test based on RFT to address non-stationarity, however, this technique requires images with a large degree of spatial smoothing, large degrees of freedom and high intensity thresholding. Recently, we proposed a voxelation-corrected 3D CST based on Gaussian random field theory that does not place constraints on the degree of spatial smoothness. However, this approach is only applicable to stationary images, requiring further modification to enable use for non-stationary images. In this study, we present modifications of this method to develop a voxelation-corrected non-stationary 3D CST based on RFT. Both simulated and real data were used to compare the voxelation-corrected non-stationary CST to the standard cluster-size adjusted non-stationary CST based on RFT and the voxelation-corrected stationary CST. We found that voxelation-corrected stationary CST is liberal for non-stationary images and the voxelation-corrected non-stationary CST performs better than cluster-size adjusted non-stationary CST based on RFT under low smoothness, low intensity threshold and low degrees of freedom.

Quantitative amide proton transfer imaging with reduced interferences from magnetization transfer asymmetry for human brain tumors at 3T.

PURPOSE: To develop a novel analysis method to evaluate quantitative amide proton transfer (qAPT) effects with reduced interference of conventional magnetization transfer effect. METHODS: A modified Z-spectrum is generated by a fitting procedure that achieves an effectively reduced magnetization transfer asymmetry. A qAPT map is then produced by subtraction of the original Z-spectrum from the modified version. This approach has been tested on both healthy volunteers and patients with brain tumors. Comparisons are made between the maps of qAPT and the commonly-used MTRasym (3.5 ppm) at different saturation powers. The negative background (NB) in MTRasym (3.5 ppm) image is recovered from the difference between the MTRasym (3.5 ppm) and qAPT maps. RESULTS: Both qAPT and MTRasym (3.5 ppm) are strongly dependent on saturation power. At a saturation power below 2 µT, the MTRasym (3.5 ppm) map is dominated by the NB rather than the APT effects for healthy brain tissue. Similar to the MTRasym (3.5 ppm) image, the qAPT image exhibits strong and robust tumor contrast. CONCLUSION: The newly-developed analysis method of qAPT is able to obtain a quantitative APT effect with less inferences from magnetization transfer asymmetry as compared to the conventional MTRasym (3.5 ppm) and can be used to evaluate human brain tumors at 3T. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc. Magn Reson Med 74:208-216, 2015. © 2014 Wiley Periodicals, Inc.