Search Results (28)

Background/Objectives: Fat and inflammation confound current magnetic resonance imaging (MRI) methods for assessing fibrosis in liver disease. Sodium or amide proton transfer-weighted MRI methods may be more specific for assessing liver fibrosis. The purpose of this study was to determine the feasibility of sodium and amide proton transfer-weighted MRI in individuals with liver disease and to determine if either method correlated with clinical markers of fibrosis. Methods: T₁ and T₂ relaxation maps, proton density fat fraction maps, liver shear stiffness maps, amide proton transfer-weighted (APTw) images, and sodium images were acquired at 3T. Image data were extracted from regions of interest placed in the liver. ANOVA tests were run with disease status, age, and body mass index as independent factors; significance was set to p < 0.05. Post-hoc t-tests were run when the ANOVA showed significance. Results: A total of 36 participants were enrolled, 34 of whom were included in the final APTw analysis and 24 in the sodium analysis. Estimated liver tissue sodium concentration differentiated participants with liver disease from those without, whereas amide proton transfer-weighted MRI did not. Estimated liver tissue sodium concentration negatively correlated with the Fibrosis-4 score, but amide proton transfer-weighted MRI did not correlate with any clinical marker of disease. Conclusions: Amide proton-weighted imaging was not different between groups. Estimated liver tissue sodium concentrations did differ between groups but did not provide additional information over conventional methods. Full article

Introduction: Sepsis-associated encephalopathy (SAE) is an acute brain dysfunction secondary to systemic infection, occurring without direct central nervous system involvement. Despite its clinical relevance, reliable biomarkers for diagnosing SAE and assessing its severity remain limited. This study aimed to evaluate the feasibility of amide proton transfer-weighted (APTw) chemical exchange saturation transfer (CEST) MRI as a non-invasive molecular imaging technique for detecting metabolic alterations related to neuroinflammation in SAE. Using a lipopolysaccharide (LPS)-induced rat model, we focused on hippocampal changes associated with neuronal inflammation. Materials and Methods: Twenty-one Sprague–Dawley rats (8 weeks old, male) were divided into three groups: control (CTRL, n = 7), LPS-induced sepsis at 5 mg/kg (LPS05, n = 7), and 10 mg/kg (LPS10, n = 7). Sepsis was induced via a single intraperitoneal injection of LPS. APTw imaging was performed using a 7 T preclinical MRI system, and signal quantification in the hippocampus was conducted using the magnetization transfer ratio asymmetry analysis. Results and Discussion: APTw imaging at 7 T demonstrated significantly elevated hippocampal APTw signals in SAE model rats (LPS05 and LPS10) compared to the control (CTRL) group: CTRL (−1.940 ± 0.207%) vs. LPS05 (−0.472 ± 0.485%) (p < 0.001) and CTRL vs. LPS10 (−0.491 ± 0.279%) (p < 0.001). However, no statistically significant difference was observed between the LPS05 and LPS10 groups (p = 0.994). These results suggest that APTw imaging can effectively detect neuroinflammation-related metabolic alterations in the hippocampus. Conclusion: Our findings support the feasibility of APTw CEST imaging as a non-invasive molecular MRI technique for SAE, with potential applications in diagnosis, disease monitoring, and therapeutic evaluation. Full article

Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid. Material & Methods: A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and APTw imaging with a 3T MR scanner. Receiver operating characteristic (ROC) curves were calculated for the APTw% mean, median, and max signal for the different molecular biomarkers. A logistic regression model was constructed for combined mean and median APTw% signals for p53 expression. Results: The whole-tumor max APTw% signal could significantly differentiate MGMTp from non-MGMTp HGG, p = 0.035. A cutoff of 4.28% max APTw% signal yielded AUC (area under the curve) = 0.702, with 70.6% sensitivity and 66.7% specificity. The mean/median APTw% signals differed significantly in p53 normal versus p53-overexpressed HGG s: 1.81%/1.83% vs. 1.15%/1.18%, p = 0.002/0.006, respectively. Cutoffs of 1.25%/1.33% for the mean/median APTw% signals yielded AUCs of 0.786/0.757, sensitivities of 76.9%/76.9%, and specificities of 50%/66.2%, p = 0.002/0.006, respectively. A logistic regression model with a combined mean and median APTw% signal for p53 status yielded an AUC = 0.788 and 76.9% sensitivity and 66.2% specificity. ATRX-, IDH- wild type (wt) vs. mutation (mut), and the level of Ki-67 did not differ significantly, but trends were found: IDH-wt and low Ki-67 showed higher mean/median/max APTw% signals vs. IDH-mut and high Ki-67, respectively. ATRX-wt vs. mutation showed higher mean and median APTw% signals but lower max APTw% signal. Conclusions: APTw imaging can potentially be a useful marker for the stratification of p53 expression and MGMT status in high-grade glioma in the preoperative setting and potentially aid surgical decision-making. Full article

Background: Differentiating brain radionecrosis (RN) from tumor progression (TP) is a persistent clinical difficulty. Here, we compared the diagnostic accuracy of leakage-corrected relative cerebral blood volume (rCBV) and fluid-suppressed amide proton transfer-weighted (APTw) imaging in distinguishing between RN and TP in metastases. Methods: Subjects with enlarging lesions after stereotactic radiosurgery were prospectively examined at 3T. APTw data were acquired with a 3D snapshot-gradient echo sequence. B0 and B1 inhomogeneities were corrected using the WASAB1 protocol. rCBV was calculated according to established guidelines. Image analysis was performed using Olea Sphere 3.0 software. ΔAPTw and ΔrCBV were calculated as the average signal within the lesion normalized against the average signal in the contralateral white matter. A diagnosis of TP or RN was assessed by histology or imaging at follow-up. Independent samples t-tests of ΔAPTw and ΔrCBV and the areas under the curve (AUCs) were computed. Results: Twenty-one metastases (10 RN, 11 TP) were evaluated. APTw differentiated between RN and TP (U = 120, p < 0.001), in contrast to rCBV (U = 71, p = 0.174). The AUC was 0.991 (95% CI = 0.962–1.020) for ΔAPTw, and 0.636 (95% CI = 0.352–0.921) for ΔrCBV. The optimal cutoff points were 0.4 and 2.1 for ΔAPTw and ΔrCBV, respectively. The sensitivity and specificity for RN-TP were 100% and 90% for ΔAPTw and 63.6% and 36.4% for ΔrCBV. Conclusions: Fluid-suppressed APTw metrics enabled more accurate diagnostic performances than leakage-corrected rCBV metrics in distinguishing between RN and TP. These promising results suggest that APTw imaging could valuably complement current multiparametric MRI protocols in brain metastases follow-ups. Full article

Amide Proton Transfer-weighted (APTw) imaging is a molecular MRI technique used to quantify protein concentrations in gliomas, which have heterogeneous components with varying cellularity and metabolic activity. This study aimed to assess the correlation between the component-specific APT signal of the neoplasm and WHO grade, molecular profile and survival status. Sixty-one patients with adult-type diffuse gliomas were retrospectively analyzed. APT values were semi-automatically extracted from tumor solid and, whenever present, necrotic components. APT values were compared between groups stratified by WHO grade, IDH-mutation, MGMT promoter methylation and 1- and 2-year survival status using Wilcoxon rank-sum test, adjusting for multiple comparisons. Overall survival (OS) was analyzed in the subgroup of 48 patients with grade 4 tumors using Cox proportional-hazards models. Random-effects models were used to assess inter-subject heterogeneity of the mean APT values in each tumor component. APT values of the solid component significantly differed between patients with grades 2–3 and 4 tumors (mean 1.58 ± 0.50 vs. 2.04 ± 0.56, p = 0.028) and correlated with OS after 1 year (1.81 ± 0.58 in survivors vs. 2.17 ± 0.51 in deceased patients, p = 0.030). APT values did not differ by IDH-mutation, MGMT methylation, and 2-year survival status. Within grade 4 glioma patients, higher APT kurtosis of the solid component was a negative prognostic factor (hazard ratio = 1.60, p = 0.040). Mean APT values of the necrosis showed high inter-subject variability, although most necrotic tumors were grade 4 and IDH wildtype. In conclusion, APTw imaging in the solid component provided metrics associated with glioma grade and survival status but showed weak correlation with IDH-mutation and MGMT promoter methylation status, in contrast to previous works. Further research is needed to understand APT signal variability within the necrotic component of high-grade gliomas. Full article

Purpose: To evaluate the amide proton transfer (APT), tumor blood flow (TBF), and apparent diffusion coefficient (ADC) combined diagnostic value for differentiating intracranial malignant tumors (MTs) from benign tumors (BTs) in young patients, as defined by the 2021 World Health Organization classification of central nervous system tumors. Methods: Fifteen patients with intracranial MTs and 10 patients with BTs aged 0–30 years underwent MRI with APT, pseudocontinuous arterial spin labeling (pCASL), and diffusion-weighted imaging. All tumors were evaluated through the use of histogram analysis and the Mann–Whitney U test to compare 10 parameters for each sequence between the groups. The diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. Results: The APT maximum, mean, 10th, 25th, 50th, 75th, and 90th percentiles were significantly higher in MTs than in BTs; the TBF minimum (min) was significantly lower in MTs than in BTs; TBF kurtosis was significantly higher in MTs than in BTs; the ADC min, 10th, and 25th percentiles were significantly lower in MTs than in BTs (all p < 0.05). The APT 50th percentile (0.900), TBF min (0.813), and ADC min (0.900) had the highest area under the curve (AUC) values of the parameters in each sequence. The AUC for the combination of these three parameters was 0.933. Conclusions: The combination of APT, TBF, and ADC evaluated through histogram analysis may be useful for differentiating intracranial MTs from BTs in young patients. Full article

Background: In the application of APTw protocols for evaluating tumors and parotid glands, inhomogeneity and hyperintensity artifacts have remained an obstacle. This study aimed to improve APTw imaging quality and evaluate the feasibility of difference B1 values to detect parotid tumors. Methods: A total of 31 patients received three APTw sequences to acquire 32 lesions and 30 parotid glands (one patient had lesions on both sides). Patients received T2WI and 3D turbo-spin-echo (TSE) APTw imaging on a 3.0 T scanner for three sequences (B1 = 2 μT, 1 μT, and 0.7 μT in APTw 1, 2, and 3, respectively). APTw image quality was evaluated using four-point Likert scales in terms of integrity and hyperintensity artifacts. Image quality was compared between the three sequences. An evaluable group and a trustable group were obtained for APTmean value comparison. Results: Tumors in both APT2 and APT3 had fewer hyperintensity artifacts than in APT1. With B1 values decreasing, tumors had less integrity in APTw imaging. APTmean values of tumors were higher than parotid glands in traditional APT1 sequence though not significant, while the APTmean subtraction value was significantly different. Conclusions: Applying a lower B1 value could remove hyperintensity but could also compromise its integrity. Combing different APTw sequences might increase the feasibility of tumor detection. Full article

Treating glioblastoma and monitoring treatment response non-invasively remain challenging. Here, we developed a robust approach using a drug-loaded liposomal hydrogel that is mechanically compatible with the brain, and, simultaneously, we successfully monitored early tumor response using Chemical Exchange Saturation Transfer (CEST) MRI. This CEST-detectable liposomal hydrogel was optimized based on a sustainable drug release and a soft hydrogel for the brain tumor, which is unfavorable for tumor cell proliferation. After injecting the hydrogel next to the tumor, three distinctive CEST contrasts enabled the monitoring of tumor response and drug release longitudinally at 3T. As a result, a continuous tumor volume decrease was observed in the treatment group along with a significant decrease in CEST contrasts relating to the tumor response at 3.5 ppm (Amide Proton Transfer; APT) and at −3.5 ppm (relayed Nuclear Overhauser Effect; rNOE) when compared to the control group (p < 0.05). Interestingly, the molecular change at 3.5 ppm on day 3 (p < 0.05) was found to be prior to the significant decrease in tumor volume on day 5. An APT signal also showed a strong correlation with the number of proliferating cells in the tumors. This demonstrated that APT detected a distinctive decrease in mobile proteins and peptides in tumors before the change in tumor morphology. Moreover, the APT signal showed a regional response to the treatment, associated with proliferating and apoptotic cells, which allowed an in-depth evaluation and prediction of the tumor treatment response. This newly developed liposomal hydrogel allows image-guided brain tumor treatment to address clinical needs using CEST MRI. Full article

Purpose: To assess the value of multimodal MRI, including amide proton transfer-weighted imaging (APT), diffusion kurtosis imaging (DKI), and T2 mapping sequences for estimating human epidermal growth factor receptor-2 (Her-2) expression in patients with endometrial cancer (EC). Methods: A total of 54 patients with EC who underwent multimodal pelvic MRI followed by biopsy were retrospectively selected and divided into the Her-2 positive (n = 24) and Her-2 negative (n = 30) groups. Her-2 expression was confirmed by immunohistochemistry (IHC). Two observers measured APT, mean kurtosis (MK), mean diffusivity (MD), and T2 values for EC lesions. Results: The Her-2 (+) group showed higher APT values and lower MD and T2 values than the Her-2 (−) group (all p < 0.05); there was no significant difference in MK values (p > 0.05). The area under the receiver operating characteristic curve (AUC) of APT, MD, T2, APT + T2, APT + MD, T2 + MD, and APT + MD + T2 models to identify the two groups of cases were 0.824, 0.695, 0.721, 0.824, 0.858, 0.782, and 0.860, respectively, and the diagnostic efficacy after combined APT + MD + T2 value was significantly higher than those of MD and T2 values individually (p = 0.018, 0.028); the diagnostic efficacy of the combination of APT + T2 values was significantly higher than that of T2 values separately (p = 0.028). Weak negative correlations were observed between APT and T2 values (r = −0.365, p = 0.007), moderate negative correlations between APT and MD values (r = −0.560, p < 0.001), and weak positive correlations between MD and T2 values (r = 0.336, p = 0.013). The APT values were independent predictors for assessing Her-2 expression in EC patients. Conclusion: The APT, DKI, and T2 mapping sequences can be used to preoperatively assess the Her-2 expression in EC, which can contribute to more precise treatment for clinical preoperative. Full article

(1) Background: Natalizumab dramatically reduces relapses and MRI inflammatory activity (new lesions and enhancing lesions) in multiple sclerosis (MS). Chemical exchange saturation transfer (CEST) MRI can explore brain tissue in vivo with high resolution and sensitivity. We investigated if natalizumab can prevent microstructural tissue damage progression measured with MRI at ultra-high field (7 Tesla) over the first year of treatment. (2) Methods: In this one-year prospective longitudinal study, patients with active relapsing–remitting MS were assessed clinically and scanned at ultra-high-field MRI at the time of their first natalizumab infusion, at 6 and 12 months, with quantitative imaging aimed to detect microstructural changes in the normal-appearing white matter (NAWM), including sequences sensitive to magnetisation transfer (MT) effects from amide proton transfer (MTRAPT) and the nuclear Overhauser effect (MTRNOE). (3) Results: 12 patients were recruited, and 10 patients completed the study. The difference in the T1 relaxation times at month 6 and month 12 of natalizumab treatment was not significant, suggesting the lack of accumulation of tissue damage, while improvements were seen in MTR (MTRAPT and MTRNOE measures) at month 12, suggesting a tissue repair effect. This paralleled the expected lack of clinical and radiological worsening of conventional MRI measures of disease activity (new lesions or gadolinium-enhancing lesions). (4) Conclusion: Natalizumab prevents microstructural brain damage and has effects suggesting an improved white matter microstructure measured at ultra-high field during the first year of treatment. Full article

Amide proton transfer (APT) and semi-solid magnetization transfer (ssMT) imaging can predict clinical outcomes in patients with glioma. However, the treatment of brain tumors is accompanied by the deposition of blood products within the tumor area in most cases. For this reason, the objective was to assess whether the diagnostic interpretation of the APT and ssMT is affected by methemoglobin (mHb) and hemosiderin (Hs) depositions at the first follow-up MRI 4 to 6 weeks after the completion of radiotherapy. A total of 34 participants underwent APT and ssMT imaging by applying reconstruction methods described by Zhou et al. (APTw_asym), Goerke et al. (MTR_RexAPT and MTR_RexMT) and Mehrabian et al. (MT_const). Contrast-enhancing tumor (CE), whole tumor (WT), mHb and Hs were segmented on contrast-enhanced T₁w_CE, T₂w-FLAIR, T₁w and T₂*w images. ROC-analysis, Kaplan–Meier analysis and the log rank test were used to test for the association of mean contrast values with therapy response and overall survival (OS) before (WT and CE) and after correcting tumor volumes for mHb and Hs (CE_C and WT_C). CE_C showed higher associations of the MTR_RexMT with therapy response (CE: AUC = 0.677, p = 0.081; CE_C: AUC = 0.705, p = 0.044) and of the APTw_asym with OS (CE: HR = 2.634, p = 0.040; CE_C: HR = 2.240, p = 0.095). In contrast, WT_C showed a lower association of the APTw_asym with survival (WT: HR = 2.304, p = 0.0849; WT_C: HR = 2.990, p = 0.020). Overall, a sophisticated correction for blood products did not substantially influence the clinical performance of APT and ssMT imaging in patients with glioma early after radiotherapy. Full article

Acidification of cancerous tissue induced pharmacologically may slow tumor growth and can be detected using magnetic resonance imaging. Numerous studies have shown that pharmacologically inhibiting specific transporters, such as the Na⁺/H⁺ exchanger 1 (NHE1), can alter glycolitic metabolism and affect tumor acidosis. The sodium proton exchanger inhibitor Cariporide can acidify U87MG gliomas in mice. This study aimed to determine whether Cariporide could acidify C6 glioma tumors in rats with an intact immune system. C6 glioma cells were implanted in the right brain hemisphere of ten rats. Chemical exchange saturation transfer (CEST) MRI (9.4T) was acquired on days 7–8 and 14–15 after implantation to measure in vivo tissue intracellular pH (pH_i) within the tumors and on the contralateral side. pH_i was basic relative to contralateral tissue at both time points assessed using the amine and amide concentration-independent detection (AACID) value. On day 14–15, measurements were made before and up to 160 min after Cariporide injection (N = 6). Twenty minutes after drug injection, the average AACID value in the tumor significantly increased by ∼6.4% compared to pre-injection, corresponding to 0.31 ± 0.20 lower pH_i, while in contralateral tissue, AACID value increased significantly by ∼4.3% compared to pre-injection, corresponding to 0.22 ± 0.19 lower pH_i. Control rats without tumors showed no changes following injection of Cariporide dissolved in 10% or 1% DMSO and diluted in PBS. This study demonstrates the sensitivity of CEST-based pH-weighted imaging for monitoring the response of tumors to pharmacologically induced acidification. Full article

The non-enhancing peritumoral area (NEPA) is defined as the hyperintense region in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images surrounding a brain tumor. The NEPA corresponds to different pathological processes, including vasogenic edema and infiltrative edema. The analysis of the NEPA with conventional and advanced magnetic resonance imaging (MRI) was proposed in the differential diagnosis of solid brain tumors, showing higher accuracy than MRI evaluation of the enhancing part of the tumor. In particular, MRI assessment of the NEPA was demonstrated to be a promising tool for distinguishing high-grade gliomas from primary lymphoma and brain metastases. Additionally, the MRI characteristics of the NEPA were found to correlate with prognosis and treatment response. The purpose of this narrative review was to describe MRI features of the NEPA obtained with conventional and advanced MRI techniques to better understand their potential in identifying the different characteristics of high-grade gliomas, primary lymphoma and brain metastases and in predicting clinical outcome and response to surgery and chemo-irradiation. Diffusion and perfusion techniques, such as diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), dynamic susceptibility contrast-enhanced (DSC) perfusion imaging, dynamic contrast-enhanced (DCE) perfusion imaging, arterial spin labeling (ASL), spectroscopy and amide proton transfer (APT), were the advanced MRI procedures we reviewed. Full article

This study aimed to evaluate an intracerebral hemorrhage (ICH) model using quantitative susceptibility mapping (QSM) and chemical exchange saturation transfer (CEST) with preclinical 7T-magnetic resonance imaging (MRI) and determine the potential of amide proton transfer-CEST (APT-CEST) for use as a biomarker for the early detection of ICH. Six Wistar male rats underwent MRI, and another six underwent histopathological examinations on postoperative days 0, 3, and 7. The ICH model was created by injecting bacterial collagenase into the right hemisphere of the brain. QSM and APT-CEST MRI were performed using horizontal 7T-MRI. Histological studies were performed to observe ICH and detect iron deposition at the ICH site. T₂-weighted images (T₂WI) revealed signal changes associated with hemoglobin degeneration in red blood cells, indicating acute-phase hemorrhage on day 0, late-subacute-phase hemorrhage on day 3, and chronic-phase hemorrhage on day 7. The susceptibility alterations in each phase were detected using QSM. QSM and Berlin blue staining revealed hemosiderin deposition in the chronic phase. APT-CEST revealed high magnetization transfer ratios in the acute phase. Abundant mobile proteins and peptides were observed in early ICH, which were subsequently diluted. APT-CEST imaging may be a reliable noninvasive biomarker for the early diagnosis of ICH. Full article

Background: The aim of this study is to investigate the feasibility of amide proton transfer-weighted (APTw) imaging combined with ZOOMit diffusion kurtosis imaging (DKI) in predicting lymph node metastasis (LNM) in cervical cancer (CC). Materials and Methods: Sixty-one participants with pathologically confirmed CC were included in this retrospective study. The APTw MRI and ZOOMit diffusion-weighted imaging (DWI) were acquired. The mean values of APTw and DKI parameters including mean kurtosis (MK) and mean diffusivity (MD) of the primary tumors were calculated. The parameters were compared between the LNM and non-LNM groups using the Student’s t-test or Mann–Whitney U test. Binary logistic regression analysis was performed to determine the association between the LNM status and the risk factors. The diagnostic performance of these quantitative parameters and their combinations for predicting the LNM was assessed with receiver operating characteristic (ROC) curve analysis. Results: Patients were divided into the LNM group (n = 17) and the non-LNM group (n = 44). The LNM group presented significantly higher APTw (3.7 ± 1.1% vs. 2.4 ± 1.0%, p < 0.001), MK (1.065 ± 0.185 vs. 0.909 ± 0.189, p = 0.005) and lower MD (0.989 ± 0.195 × 10⁻³ mm²/s vs. 1.193 ± 0.337 ×10⁻³ mm²/s, p = 0.035) than the non-LNM group. APTw was an independent predictor (OR = 3.115, p = 0.039) for evaluating the lymph node status through multivariate analysis. The area under the curve (AUC) of APTw (0.807) was higher than those of MK (AUC, 0.715) and MD (AUC, 0.675) for discriminating LNM from non-LNM, but the differences were not significant (all p > 0.05). Moreover, the combination of APTw, MK, and MD yielded the highest AUC (0.864), with the corresponding sensitivity of 76.5% and specificity of 88.6%. Conclusion: APTw and ZOOMit DKI parameters may serve as potential noninvasive biomarkers in predicting LNM of CC. Full article