CEST-MRI for body oncologic imaging: are we there yet?

Chemical exchange saturation transfer (CEST) MRI has gained recognition as a valuable addition to the molecular imaging and quantitative biomarker arsenal, especially for characterization of brain tumors. There is also increasing interest in the use of CEST-MRI for applications beyond the brain. However, its translation to body oncology applications lags behind those in neuro-oncology. The slower migration of CEST-MRI to non-neurologic applications reflects the technical challenges inherent to imaging of the torso. In this review, we discuss the application of CEST-MRI to oncologic conditions of the breast and torso (i.e., body imaging), emphasizing the challenges and potential solutions to address them. While data are still limited, reported studies suggest that CEST signal is associated with important histology markers such as tumor grade, receptor status, and proliferation index, some of which are often associated with prognosis and response to therapy. However, further technical development is still needed to make CEST a reliable clinical application for body imaging and establish its role as a predictive and prognostic biomarker.

Accelerating chemical exchange saturation transfer MRI with parallel blind compressed sensing.

PURPOSE: Chemical exchange saturation transfer is a novel and promising MRI contrast method, but it can be time-consuming. Common parallel imaging methods, like SENSE, can lead to reduced quality of CEST. Here, parallel blind compressed sensing (PBCS), combining blind compressed sensing (BCS) and parallel imaging, is evaluated for the acceleration of CEST in brain and breast. METHODS: The CEST data were collected in phantoms, brain (N = 3), and breast (N = 2). Retrospective Cartesian undersampling was implemented and the reconstruction results of PBCS-CEST were compared with BCS-CEST and k-t sparse-SENSE CEST. The normalized RMSE and the high-frequency error norm were used for quantitative comparison. RESULTS: In phantom and in vivo brain experiments, the acceleration factor of R = 10 (24 k-space lines) was achieved and in breast R = 5 (30 k-space lines), without compromising the quality of the PBCS-reconstructed magnetization transfer rate asymmetry maps and Z-spectra. Parallel BCS provides better reconstruction quality when compared with BCS, k-t sparse-SENSE, and SENSE methods using the same number of samples. Parallel BCS overperforms BCS, indicating that the inclusion of coil sensitivity improves the reconstruction of the CEST data. CONCLUSION: The PBCS method accelerates CEST without compromising its quality. Compressed sensing in combination with parallel imaging can provide a valuable alternative to parallel imaging alone for accelerating CEST experiments.

Prospective acceleration of parallel RF transmission-based 3D chemical exchange saturation transfer imaging with compressed sensing.

PURPOSE: To develop prospectively accelerated 3D CEST imaging using compressed sensing (CS), combined with a saturation scheme based on time-interleaved parallel transmission. METHODS: A variable density pseudo-random sampling pattern with a centric elliptical k-space ordering was used for CS acceleration in 3D. Retrospective CS studies were performed with CEST phantoms to test the reconstruction scheme. Prospectively CS-accelerated 3D-CEST images were acquired in 10 healthy volunteers and 6 brain tumor patients with an acceleration factor (RCS ) of 4 and compared with conventional SENSE reconstructed images. Amide proton transfer weighted (APTw) signals under varied RF saturation powers were compared with varied acceleration factors. RESULTS: The APTw signals obtained from the CS with acceleration factor of 4 were well-preserved as compared with the reference image (SENSE R = 2) both in retrospective phantom and prospective healthy volunteer studies. In the patient study, the APTw signals were significantly higher in the tumor region (gadolinium [Gd]-enhancing tumor core) than in the normal tissue (p < .001). There was no significant APTw difference between the CS-accelerated images and the reference image. The scan time of CS-accelerated 3D APTw imaging was dramatically reduced to 2:10 minutes (in-plane spatial resolution of 1.8 × 1.8 mm2 ; 15 slices with 4-mm slice thickness) as compared with SENSE (4:07 minutes). CONCLUSION: Compressed sensing acceleration was successfully extended to 3D-CEST imaging without compromising CEST image quality and quantification. The CS-based CEST imaging can easily be integrated into clinical protocols and would be beneficial for a wide range of applications.

Histogram analysis of amide proton transfer-weighted imaging: comparison of glioblastoma and solitary brain metastasis in enhancing tumors and peritumoral regions.

OBJECTIVES: Differentiation of glioblastomas (GBMs) and solitary brain metastases (SBMs) is an important clinical problem. The aim of this study was to determine whether amide proton transfer-weighted (APTW) imaging is useful for distinguishing GBMs from SBMs. METHODS: We examined 31 patients with GBM and 17 with SBM. For each tumor, enhancing areas (EAs) and surrounding non-enhancing areas with T2-prolongation (peritumoral high signal intensity areas, PHAs) were manually segmented using fusion images of the post-contrast T1-weighted and T2-weighted images. The mean amide proton transfer signal intensities (APTSIs) were compared among the EAs, PHAs, and contralateral normal appearing white matter (NAWM) within each tumor type. Furthermore, we analyzed APTSI histograms to compare the EAs and PHAs of GBMs and SBMs. RESULTS: In GBMs, the mean APTSI in EAs (2.92 ± 0.74%) was the highest, followed by that in PHAs (1.64 ± 0.83%, p < 0.001) and NAWM (0.43 ± 0.83%, p < 0.001). In SBMs, the mean APTSI in EAs (1.85 ± 0.99%) and PHAs (1.42 ± 0.45%) were significantly higher than that in NAWM (0.42 ± 0.30%, p < 0.001), whereas no significant difference was found between EAs and PHAs. The mean and 10th, 25th, 50th, 75th, and 90th percentiles for APT in EAs of GBMs were significantly higher than those of SBMs. However, no significant difference was found between GBMs and SBMs in any histogram parameters for PHA. CONCLUSIONS: APTSI in EAs, but not PHAs, is useful for differentiation between GBMs and SBMs. KEY POINTS: • Amide proton transfer-weighted imaging and histogram analysis in the enhancing tumor can provide useful information for differentiation between glioblastomas and solitary brain metastasis. • Amide proton transfer signal intensity histogram parameters from peritumoral areas showed no significant difference between glioblastomas and solitary brain metastasis. • Vasogenic edema alone can substantially increase amide proton transfer signal intensity which may mimic tumor invasion.

Amide proton transfer imaging to predict tumor response to neoadjuvant chemotherapy in locally advanced rectal cancer.

BACKGROUND AND AIM: The amount of proteins and peptides can be estimated with amide proton transfer (APT) imaging. Previous studies demonstrated the usefulness of APT imaging to predict tumor malignancy. We determined whether APT imaging can predict the tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced rectal cancer (LARC). METHODS: Seventeen patients with LARC who underwent a pretherapeutic magnetic resonance examination including APT imaging and NAC (at least two courses) were enrolled. The APT-weighted imaging (WI) signal intensity (SI) (%) was defined as magnetization transfer ratio asymmetry (MTRasym ) at the offset of 3.5 ppm. Each tumor was histologically evaluated for the degree of degeneration and necrosis and then classified as one of five histological Grades (0, none; 1a, less than 1/3; 1b, 1/3 to 2/3; 2, more than 2/3; 3, all). We compared the mean APTWI SIs of the tumors between the Grade 0/1a/1b (low-response group) and Grade 2/3 (high-response group) by Student's t-test. We used receiver operating characteristics curves to determine the diagnostic performance of the APTWI SI for predicting the tumor response. RESULTS: The mean APTWI SI of the low-response group (n = 12; 3.05 ± 1.61%) was significantly higher than that of the high-response group (n = 5; 1.14 ± 1.13%) (P = 0.029). The area under the curve for predicting the tumor response using the APTWI SI was 0.87. When ≥2.75% was used as an indicator of low-response status, 75% sensitivity and 100% specificity of the APTWI SI were obtained. CONCLUSION: Pretherapeutic APT imaging can predict the tumor response to NAC in patients with LARC.

Amide Proton Transfer MR Imaging of Endometrioid Endometrial Adenocarcinoma: Association with Histologic Grade.

Purpose To evaluate the utility of amide proton transfer (APT) imaging in estimating histologic grades of endometrioid endometrial adenocarcinoma (EEA). Materials and Methods The institutional review board approved this prospective study. Between June 2012 and March 2016, 32 patients with EEA underwent magnetic resonance (MR) imaging. After their surgical procedures, their EEAs were confirmed pathologically and classified into histologic grades: grade 1 (n = 11), grade 2 (n = 11), and grade 3 (n = 10). The APT signal intensities (SIs) and the mean and minimum apparent diffusion coefficients (ADCs) of the three grades were calculated and compared. Spearman rank correlation coefficient was also calculated between the APT SIs and histologic grades, and between the ADCs and histologic grades. Results The Spearman correlation coefficient with histologic grade of the APT SIs, the mean ADC, and the minimum ADC were 0.55 (P = .001), 0.03 (P = .84), and -0.30 (P = .09), respectively. The average APT SIs and the mean and minimum ADCs were 2.2% ± 0.2 (standard deviation), 0.9 × 10-3 mm2/sec ± 0.2, and 0.6 × 10-3 mm2/sec ± 0.1 for grade 1; 3.2% ± 0.3, 0.8 × 10-3 mm2/sec ± 0.1, and 0.5 × 10-3 mm2/sec ± 0.1 for grade 2; and 3.7% ± 0.3, 0.9 × 10-3 mm2/sec ± 0.1, and 0.5 × 10-3 mm2/sec ± 0.1 for grade 3, respectively. The APT SIs of grade 3 EEA were significantly higher than those of grade 1 EEA (P = .01), but other pairwise comparisons did not reveal any significant differences (P = .06-.51). The mean and minimum ADCs showed no significant differences among the three histologic grades (P =.13-.51). Conclusion The APT SI was positively correlated with the histologic grades of EEA. © RSNA, 2017 Online supplemental material is available for this article.

Z-spectrum appearance and interpretation in the presence of fat: Influence of acquisition parameters.

PURPOSE: Chemical exchange saturation transfer (CEST) MRI is increasingly evolving from brain to body applications. One of the known problems in the body imaging is the presence of strong lipid signals. Although their influence on the CEST effect is acknowledged, there was no study that focuses on the interplay among echo time, fat fraction, and Z-spectrum. This study strives to address these points, with the emphasis on the application in the breast. METHODS: Z-spectra were simulated in phase and out of phase of the main fat peak at -3.4 ppm, with the fat fraction varying from 0 to 100%. The magnetization transfer ratio asymmetry in two ranges, centering at the exchanging pool and at 3.5 ppm approximately opposite the nonexchanging fat pool, were calculated and were plotted against fat fraction. The results were verified in phantoms and in vivo. RESULTS: The results demonstrate the combined influence of fat fraction and echo time on the Z-spectrum for gradient echo based CEST acquisitions. The influence is straightforward in the in-phase images, but it is more complicated in the out-of-phase images, potentially leading to erroneous CEST contrast. CONCLUSIONS: This study provides a basis for understanding the origin and appearance of lipid artifacts in CEST imaging, and lays the foundation for their efficient removal. Magn Reson Med 79:2731-2737, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Amide proton transfer imaging seems to provide higher diagnostic performance in post-treatment high-grade gliomas than methionine positron emission tomography.

OBJECTIVES: To compare the diagnostic performance of amide proton transfer (APT) imaging and 11-C methionine positron emission tomography (MET-PET) for in vivo molecular imaging of protein metabolism in post-treatment gliomas. MATERIALS AND METHODS: This study included 43 patients (12 low and 31 high grade) with post-treatment gliomas who underwent both APT and MET-PET imaging within 3 weeks. APT-weighted voxel values and semi-quantitative tumour-to-normal ratios (TNR) were obtained from tumour portions. The voxel-wise relationships between TNR and APT were assessed. The diagnostic performance for recurrence of high-grade gliomas was calculated, using the area under the receiver operating characteristic curve (AUC) with maximum (TNRmax and APTmax) and 90% histogram values (TNR90 and APT90). RESULTS: A moderate positive correlation between TNR and APT was found in low-grade recurrences (r = 0.47, p < 0.001), but not in high-grade ones (r = -0.24, p < 0.001). For distinguishing recurrence in post-treatment high-grade gliomas, APTmax (AUC, 0.88) and APT90 (AUC, 0.78-0.83) had a similar to better diagnostic performance than TNRmax (AUC, 0.71, p = 0.08) or TNR90 (AUC, 0.53-0.59, p = 0.01-0.05). CONCLUSIONS: In post-treatment high-grade gliomas, APT provides different regional information to MET-PET and provides higher diagnostic performance. This difference needs to be considered when using APT or MET-PET as a surrogate marker for tumour protein metabolism. KEY POINTS: • APT and TNR values in low-grade recurrence showed a moderate voxel-wise correlation. • APT and TNR demonstrated regional differences in post-treatment high-grade gliomas. • APT90 showed better diagnostic performance than TNR90 in high-grade recurrence.

Amide proton transfer imaging of brain tumors using a self-corrected 3D fast spin-echo dixon method: Comparison With separate B0 correction.

PURPOSE: To assess the quantitative performance of three-dimensional (3D) fast spin-echo (FSE) Dixon amide proton transfer (APT) imaging of brain tumors compared with B0 correction with separate mapping methods. METHODS: Twenty-two patients with brain tumors (54.2 ± 18.7 years old, 12 males and 10 females) were scanned at 3 Tesla (T). Z-spectra were obtained at seven different frequency offsets at ±3.1 ppm, ± 3.5 ppm, ± 3.9 ppm, and -1560 ppm. The scan was repeated three times at +3.5 ppm with echo shifts for Dixon B0 mapping. The APT image corrected by a three-point Dixon-type B0 map from the same scan (3D-Dixon) or a separate B0 map (2D-separate and 3D-separate), and an uncorrected APT image (3D-uncorrected) were generated. We compared the APT-weighted signals within a tumor obtained with each 3D method with those obtained with 2D-separate as a reference standard. RESULTS: Excellent agreements and correlations with the 2D-separate were obtained by the 3D-Dixon method for both mean (ICC = 0.964, r = 0.93, P < 0.0001) and 90th-percentile (ICC = 0.972, r = 0.95, P < 0.0001) APT-weighted signals. These agreements and correlations for 3D-Dixon were better than those obtained by the 3D-uncorrected and 3D-separate methods. CONCLUSION: The 3D FSE Dixon APT method with intrinsic B0 correction offers a quantitative performance that is similar to that of established two-dimensional (2D) methods. Magn Reson Med 77:2272-2279, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Optimal high b-value for diffusion weighted MRI in diagnosing high risk prostate cancers in the peripheral zone.

PURPOSE: To retrospectively determine the optimal b-value(s) of diffusion-weighted imaging (DWI) associated with intermediate-high risk cancer in the peripheral zone (PZ) of the prostate. MATERIALS AND METHODS: Forty-two consecutive patients underwent multi b-value (16 evenly spaced b-values between 0 and 2000 s/mm2 ) DWI along with multi-parametric MRI (MP-MRI) of the prostate at 3 Tesla followed by trans-rectal ultrasound/MRI fusion guided targeted biopsy of suspicious lesions detected at MP-MRI. Computed DWI images up to a simulated b-value of 4000 s/mm2 were also obtained using a pair of b-values (b = 133 and 400 or 667 or 933 s/mm2 ) from the multi b-value DWI. The contrast ratio of average intensity of the targeted lesions and the background PZ was determined. Receiver operator characteristic curves and the area under the curve (AUCs) were obtained for separating patients eligible for active surveillance with low risk prostate cancers from intermediate-high risk prostate cancers as per the cancer of the prostate risk assessment (CAPRA) scoring system. RESULTS: The AUC first increased then decreased with the increase in b-values reaching maximum at b = 1600 s/mm2 (0.74) with no statistically significant different AUC of DWI with b-values 1067-2000 s/mm2 . The AUC of computed DWI increased then decreased with the increase in b-values reaching a maximum of 0.75 around b = 2000 s/mm2 . There was no statistically significant difference between the AUC of optimal acquired DWI and either of optimal computed DWI. CONCLUSION: The optimal b-value for acquired DWI in differentiating intermediate-high from low risk prostate cancers in the PZ is b = 1600 s/mm2 . The computed DWI has similar performance as that of acquired DWI with the optimal performance around b = 2000 s/mm2 . LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;45:125-131.

Grading diffuse gliomas without intense contrast enhancement by amide proton transfer MR imaging: comparisons with diffusion- and perfusion-weighted imaging.

OBJECTIVES: To investigate whether amide proton transfer (APT) MR imaging can differentiate high-grade gliomas (HGGs) from low-grade gliomas (LGGs) among gliomas without intense contrast enhancement (CE). METHODS: This retrospective study evaluated 34 patients (22 males, 12 females; age 36.0 ± 11.3 years) including 20 with LGGs and 14 with HGGs, all scanned on a 3T MR scanner. Only tumours without intense CE were included. Two neuroradiologists independently performed histogram analyses to measure the 90th-percentile (APT90) and mean (APTmean) of the tumours' APT signals. The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were also measured. The parameters were compared between the groups with Student's t-test. Diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis. RESULTS: The APT90 (2.80 ± 0.59 % in LGGs, 3.72 ± 0.89 in HGGs, P = 0.001) and APTmean (1.87 ± 0.49 % in LGGs, 2.70 ± 0.58 in HGGs, P = 0.0001) were significantly larger in the HGGs compared to the LGGs. The ADC and rCBV values were not significantly different between the groups. Both the APT90 and APTmean showed medium diagnostic performance in this discrimination. CONCLUSIONS: APT imaging is useful in discriminating HGGs from LGGs among diffuse gliomas without intense CE. KEY POINTS: • Amide proton transfer (APT) imaging helps in grading non-enhancing gliomas • High-grade gliomas showed higher APT signal than low-grade gliomas • APT imaging showed better diagnostic performance than diffusion- and perfusion-weighted imaging.

Amide proton transfer (APT) magnetic resonance imaging of prostate cancer: comparison with Gleason scores.

OBJECTIVE: To evaluate the utility of amide proton transfer (APT) imaging in estimating the Gleason score (GS) of prostate cancer (Pca). MATERIALS AND METHODS: Sixty-six biopsy-proven cancers were categorized into four groups according to the GS: GS-6 (3 + 3); GS-7 (3 + 4/4 + 3); GS-8 (4 + 4) and GS-9 (4 + 5/5 + 4). APT signal intensities (APT SIs) and apparent diffusion coefficient (ADC) values of each GS group were compared by one-way analysis of variance with Tukey's HSD post hoc test. RESULTS: The mean and standard deviation of the APT SIs (%) and ADC values (×10(-3) mm(2)/s) were as follows: GS-6, 2.48 ± 0.59 and 1.16 ± 0.26; GS-7, 5.17 ± 0.66 and 0.92 ± 0.18; GS-8, 2.56 ± 0.85 and 0.86 ± 0.17; GS-9, 1.96 ± 0.75 and 0.85 ± 0.18, respectively. The APT SI of the GS-7 group was highest, and there were significant differences between the GS-6 and GS-7 groups and the GS-7 and GS-9 groups (p < 0.05). The ADC value of the GS-6 group was significantly higher than each value of the GS-7, GS-8, and GS-9 groups (p < 0.05), but no significant differences were obtained among the GS-7, GS-8, and GS-9 groups. CONCLUSION: The mean APT SI in Pca with a GS of 7 was higher than that for the other GS groups.

Angiogenesis and airway reactivity in asthmatic Brown Norway rats.

Expanded and aberrant bronchial vascularity, a prominent feature of the chronic asthmatic airway, might explain persistent airway wall edema and sustained leukocyte recruitment. Since it is well established that there are causal relationships between exposure to house dust mite (HDM) and the development of asthma, determining the effects of HDM in rats, mammals with a bronchial vasculature similar to humans, provides an opportunity to study the effects of bronchial angiogenesis on airway function directly. We studied rats exposed bi-weekly to HDM (Der p 1; 50 µg/challenge by intranasal aspiration, 1, 2, 3 weeks) and measured the time course of appearance of increased blood vessels within the airway wall. Results demonstrated that within 3 weeks of HDM exposure, the number of vessels counted within airway walls of bronchial airways (0.5-3 mm perimeter) increased significantly. These vascular changes were accompanied by increased airway responsiveness to methacholine. A shorter exposure regimen (2 weeks of bi-weekly exposure) was insufficient to cause a significant increase in functional vessels or reactivity. Yet, 19F/1H MR imaging at 3T following αvß3-targeted perfluorocarbon nanoparticle infusion revealed a significant increase in 19F signal in rat airways after 2 weeks of bi-weekly HDM, suggesting earlier activation of the process of neovascularization. Although many antigen-induced mouse models exist, mice lack a bronchial vasculature and consequently lack the requisite human parallels to study bronchial edema. Overall, our results provide an important new model to study the impact of bronchial angiogenesis on chronic inflammation and airways hyperreactivity.

Balanced UTE-SSFP for 19F MR imaging of complex spectra.

PURPOSE: A novel technique for highly sensitive detection of multiresonant fluorine imaging agents was designed and tested with the use of dual-frequency 19F/1H ultrashort echo times (UTE) sampled with a balanced steady-state free precession (SSFP) pulse sequence and three-dimensional (3D) radial readout. METHODS: Feasibility of 3D radial balanced UTE-SSFP imaging was demonstrated for a phantom comprising liquid perfluorooctyl bromide (PFOB). Sensitivity of the pulse sequence was measured and compared with other sequences imaging the PFOB (CF2 )6 line group including UTE radial gradient-echo (GRE) at α = 30°, as well as Cartesian GRE, balanced SSFP, and fast spin-echo (FSE). The PFOB CF3 peak was also sampled with FSE. RESULTS: The proposed balanced UTE-SSFP technique exhibited a relative detection sensitivity of 51 µmolPFOB(-1) min(-1/2) (α = 30°), at least twice that of other sequence types with either 3D radial (UTE GRE: 20 µmolPFOB(-1) min(-1/2) ) or Cartesian k-space filling (GRE: 12 µmolPFOB(-1) min(-1/2) ; FSE: 16 µmolPFOB(-1) min(-1/2) ; balanced SSFP: 23 µmolPFOB(-1) min(-1/2) ). In vivo imaging of angiogenesis-targeted PFOB nanoparticles was demonstrated in a rabbit model of cancer on a clinical 3 Tesla scanner. CONCLUSION: A new dual 19F/1H balanced UTE-SSFP sequence manifests high SNR, with detection sensitivity more than two-fold better than traditional techniques, and alleviates imaging problems caused by dephasing in complex spectra.

Multiparametric MRI analysis for the evaluation of MR-guided high intensity focused ultrasound tumor treatment.

For the clinical application of high intensity focused ultrasound (HIFU) for thermal ablation of malignant tumors, accurate treatment evaluation is of key importance. In this study, we have employed a multiparametric MRI protocol, consisting of quantitative T1, T2, ADC, amide proton transfer (APT), T1ρ and DCE-MRI measurements, to evaluate MR-guided HIFU treatment of subcutaneous tumors in rats. K-means clustering using all different combinations of the endogenous contrast MRI parameters (feature vectors) was performed to segment the multiparametric data into tissue populations with similar MR parameter values. The optimal feature vector for identification of the extent of non-viable tumor tissue after HIFU treatment was determined by quantitative comparison between clustering-derived and histology-derived non-viable tumor fractions. The highest one-to-one correspondence between these clustering-based and histology-based non-viable tumor fractions was observed for the feature vector {ADC, APT-weighted signal} (R(2) to line of identity (R(2)y=x) = 0.92) and the strongest agreement was seen 3 days after HIFU (R(2)y=x = 0.97). To compare the multiparametric MRI analysis results with conventional HIFU monitoring and evaluation methods, the histology-derived non-viable tumor fractions were also quantitatively compared with non-perfused tumor fractions (derived from the level of contrast enhancement in the DCE-MRI measurements) and 240 CEM tumor fractions (i.e. thermal dose > 240 cumulative equivalent minutes at 43 °C). The correlation between histology-derived non-viable tumor fractions directly after HIFU and the 240 CEM fractions was high, but not significant. The non-perfused fractions overestimated the extent of non-viable tumor tissue directly after HIFU, whereas an underestimation was observed 3 days after HIFU. In conclusion, we have shown that a multiparametric MR analysis, especially based on the ADC and the APT-weighted signal, can potentially be used to determine the extent of non-viable tumor tissue 3 days after HIFU treatment. We expect that this method can be incorporated in the current clinical workflow of MR-HIFU ablation therapies.

Scan-rescan reproducibility of parallel transmission based amide proton transfer imaging of brain tumors.

PURPOSE: To evaluate the reproducibility of amide proton transfer (APT) imaging of brain tumors using a parallel transmission-based technique. MATERIALS AND METHODS: Thirteen patients with brain tumors (four low-grade gliomas, three glioblastoma multiforme, five meningiomas, and one malignant lymphoma) were included in the study. APT imaging was conducted at 3T using a 2-channel parallel transmission scheme with a saturation time of 2 seconds and B1 amplitude of 2 µT. A 2D fast spin-echo sequence with driven-equilibrium refocusing was used for imaging. Z-spectra were obtained at 25 frequency offsets from -6 to +6 ppm (step 0.5 ppm). A point-by-point B0 correction was performed with a B0 map. A scan-rescan reproducibility test was performed in two sessions on separate days for each patient. The interval between the two sessions was 4.8 ± 3.5 days. Regions-of-interest (ROIs) were placed to include the whole tumor for each case. A mean and 90-percentile value of APT signal for the whole tumor histogram was calculated for each session. The between-session and within-session reproducibility was evaluated using linear regression analysis, intraclass correlation coefficient (ICC), and a Bland-Altman plot. RESULTS: The mean and 90-percentile values of the APT signal for whole tumor ROI showed excellent agreements between the two sessions, with R(2) of 0.91 and 0.96 in the linear regression analysis and ICC of 0.95 and 0.97, respectively. CONCLUSION: Parallel transmission-based APT imaging of brain tumors showed good reproducibility.

Characterization of early neovascular response to acute lung ischemia using simultaneous (19)F/ (1)H MR molecular imaging.

Angiogenesis is an important constituent of many inflammatory pulmonary diseases, which has been unappreciated until recently. Early neovascular expansion in the lungs in preclinical models and patients is very difficult to assess noninvasively, particularly quantitatively. The present study demonstrated that (19)F/(1)H MR molecular imaging with αvß3-targeted perfluorocarbon nanoparticles can be used to directly measure neovascularity in a rat left pulmonary artery ligation (LPAL) model, which was employed to create pulmonary ischemia and induce angiogenesis. In rats 3 days after LPAL, simultaneous (19)F/(1)H MR imaging at 3T revealed a marked (19)F signal in animals 2 h following αvß3-targeted perfluorocarbon nanoparticles [(19)F signal (normalized to background) = 0.80 ± 0.2] that was greater (p = 0.007) than the non-targeted (0.30 ± 0.04) and the sham-operated (0.07 ± 0.09) control groups. Almost no (19)F signal was found in control right lung with any treatment. Competitive blockade of the integrin-targeted particles greatly decreased the (19)F signal (p = 0.002) and was equivalent to the non-targeted control group. Fluorescent and light microscopy illustrated heavy decorating of vessel walls in and around large bronchi and large pulmonary vessels. Focal segmental regions of neovessel expansion were also noted in the lung periphery. Our results demonstrate that (19)F/(1)H MR molecular imaging with αvß3-targeted perfluorocarbon nanoparticles provides a means to assess the extent of systemic neovascularization in the lung.

MR cholangiography demonstrates unsuspected rapid biliary clearance of nanoparticles in rodents: implications for clinical translation.

Due to their small size, lower cost, short reproduction cycle, and genetic manipulation, rodents have been widely used to test the safety and efficacy for pharmaceutical development in human disease. In this report, MR cholangiography demonstrated an unexpected rapid (<5 min) biliary elimination of gadolinium-perfluorocarbon nanoparticles (approximately 250 nm diameter) into the common bile duct and small intestine of rats, which is notably different from nanoparticle clearance patterns in larger animals and humans. Unawareness of this dissimilarity in nanoparticle clearance mechanisms between small animals and humans may lead to fundamental errors in predicting nanoparticle efficacy, pharmacokinetics, biodistribution, bioelimination, and toxicity. From the clinical editor: Comprehensive understanding of nanoparticle clearance is a clear prerequisite for human applications of nanomedicine-based therapeutic approaches. Through a novel use of MR cholangiography, this study demonstrates unusually rapid hepatic clearance of gadolinium-perfluorocarbon nanoparticles in rodents, in a pattern that is different than what is observed in larger animals and humans, raising awareness of important differences between common rodent-based models and larger mammals.

Estimation of effective b-value for a diffusion-weighted double-echo steady-state sequence with bipolar gradients.

Diffusion-weighted double-echo steady-state (dwDESS) MRI with bipolar diffusion gradients is a promising candidate to obtain diffusion weighted images (DWI) free of geometric distortions and with low motion sensitivity. However, a wider clinical application of dwDESS is currently hindered as no method is reported to explicitly calculate the effective b-value of the obtained DWI from the diffusion-gradients applied in the sequence. To this end, a previously described signal model was adapted for dwDESS with bipolar diffusion gradients, which allows to estimate an effective b-value, dubbed b'. Evaluation in phantom examinations was performed on a clinical 1.5 T MR system. Experimental results were compared with theoretical predictions, including the apparent diffusion coefficient (ADC) based on b-values from a standard EPI-DWI sequence and ADC' based on the effective b' from the dwDESS sequence. The adapted signal model was able to describe the experimental results, and the obtained values of ADC' were in line with conventional ADC measurements.