Search Results (20)

Introduction: Substance use disorders (SUDs) pose a significant public health challenge, with current treatments often exhibiting limited effectiveness and high relapse rates. Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique that delivers low-intensity direct current via scalp electrodes, has shown promise in various psychiatric and neurological conditions. In SUDs, tDCS may help to modulate key neurocircuits involved in craving, executive control, and reward processing, potentially mitigating compulsive drug use. However, the precise neurobiological mechanisms by which tDCS exerts its therapeutic effects in SUDs remain only partly understood. This review addresses that gap by synthesizing evidence from clinical studies that used neuroimaging (fMRI, fNIRS, EEG) and blood-based biomarkers to elucidate tDCS’s mechanisms in treating SUDs. Methods: A targeted literature search identified articles published between 2008 and 2024 investigating tDCS interventions in alcohol, nicotine, opioid, and stimulant use disorders, focusing specifically on physiological and neurobiological assessments rather than purely behavioral outcomes. Studies were included if they employed either neuroimaging (fMRI, fNIRS, EEG) or blood tests (neurotrophic and neuroinflammatory markers) to investigate changes induced by single- or multi-session tDCS. Two reviewers screened titles/abstracts, conducted full-text assessments, and extracted key data on participant characteristics, tDCS protocols, neurobiological measures, and clinical outcomes. Results: Twenty-seven studies met the inclusion criteria. Across fMRI studies, tDCS—especially targeting the dorsolateral prefrontal cortex—consistently modulated large-scale network activity and connectivity in the default mode, salience, and executive control networks. Many of these changes correlated with subjective craving, attentional bias, or extended time to relapse. EEG-based investigations found that tDCS can alter event-related potentials (e.g., P3, N2, LPP) linked to inhibitory control and salience processing, often preceding or accompanying changes in craving. One fNIRS study revealed enhanced connectivity in prefrontal regions under active tDCS. At the same time, two blood-based investigations reported the partial normalization of neurotrophic (BDNF) and proinflammatory markers (TNF-α, IL-6) in participants receiving tDCS. Multi-session protocols were more apt to drive clinically meaningful neuroplastic changes than single-session interventions. Conclusions: Although significant questions remain regarding optimal stimulation parameters, sample heterogeneity, and the translation of acute neural shifts into lasting behavioral benefits, this research confirms that tDCS can induce detectable neurobiological effects in SUD populations. By reshaping activity across prefrontal and reward-related circuits, modulating electrophysiological indices, and altering relevant biomarkers, tDCS holds promise as a viable, mechanism-based adjunctive therapy for SUDs. Rigorous, large-scale studies with longer follow-up durations and attention to individual differences will be essential to establish how best to harness these neuromodulatory effects for durable clinical outcomes. Full article

Brain connectivity represents the functional organization of the brain, which is an important indicator for evaluating neuropsychiatric disorders and treatment effects. Schizophrenia is associated with impaired functional connectivity but characterizing the complex abnormality patterns has been challenging. In this work, we used resting-state functional magnetic resonance imaging (fMRI) data to measure functional connectivity between 55 schizophrenia patients and 63 healthy controls across 246 regions of interest (ROIs) and extracted the disease-related connectivity patterns using energy landscape (EL) analysis. EL analysis captures the complexity of brain function in schizophrenia by focusing on functional brain state stability and region-specific dynamics. Age, sex, and smoker demographics between patients and controls were not significantly different. However, significant patient and control differences were found for the brief psychiatric rating scale (BPRS), auditory perceptual trait and state (APTS), visual perceptual trait and state (VPTS), working memory score, and processing speed score. We found that the brains of individuals with schizophrenia have abnormal energy landscape patterns between the right and left rostral lingual gyrus, and between the left lateral and orbital area in 12/47 regions. The results demonstrate the potential of the proposed imaging analysis workflow to identify potential connectivity biomarkers by indexing specific clinical features in schizophrenia patients. 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

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

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

To investigate whether parameters from IDEAL-IQ/amide proton transfer MRI (APTWI) could help predict histopathological factors of rectal cancer. Preoperative IDEAL-IQ and APTWI sequences of 67 patients with rectal cancer were retrospectively analyzed. The intra-tumoral proton density fat fraction (PDFF), R2* and magnetization transfer ratio asymmetry (MTRasym (3.5 ppm)) were measured according to the histopathological factors of rectal cancer. The relationship between MR parameters and histopathological factors were analyzed, along with diagnostic performance of MR parameters. PDFF, R2* and MTRasym (3.5 ppm) were statistically different between T1+T2/T3+T4 stages, non-metastatic/metastatic lymph nodes, lower/higher tumor grade and negative/positive status of MRF and EMVI (p < 0.001 for PDFF, p = 0.000–0.015 for R2* and p = 0.000–0.006 for MTRasym (3.5 ppm)). There were positive correlations between the above parameters and the histopathological features of rectal cancer (r = 0.464–0.723 for PDFF (p < 0.001), 0.299–0.651 for R2* (p = 0.000–0.014), and 0.337–0.667 for MTRasym (3.5 ppm) (p = 0.000–0.005)). MTRasym (3.5 ppm) correlated moderately and mildly with PDFF (r = 0.563, p < 0.001) and R2* (r = 0.335, p = 0.006), respectively. PDFF provided a significantly higher diagnostic ability than MTRasym (3.5 ppm) for distinguishing metastatic from non-metastatic lymph nodes (z = 2.407, p = 0.0161). No significant differences were found in MR parameters for distinguishing other histopathological features (p > 0.05). IDEAL-IQ and APTWI were associated with histopathological factors of rectal cancer, and might serve as non-invasive biomarkers for characterizing rectal cancer. 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

Chemical exchange saturation transfer (CEST) is a molecular magnetic resonance imaging (MRI) method that can generate image contrast based on the proton exchange between labeled protons in solutes and free, bulk water protons. Amide proton transfer (APT) imaging is the most frequently reported amide-proton-based CEST technique. It generates image contrast by reflecting the associations of mobile proteins and peptides resonating at 3.5 ppm downfield from water. Although the origin of the APT signal intensity in tumors is unclear, previous studies have suggested that the APT signal intensity is increased in brain tumors due to the increased mobile protein concentrations in malignant cells in association with an increased cellularity. High-grade tumors, which demonstrate a higher proliferation than low-grade tumors, have higher densities and numbers of cells (and higher concentrations of intracellular proteins and peptides) than low-grade tumors. APT-CEST imaging studies suggest that the APT-CEST signal intensity can be used to help differentiate between benign and malignant tumors and high-grade gliomas and low-grade gliomas as well as estimate the nature of lesions. In this review, we summarize the current applications and findings of the APT-CEST imaging of various brain tumors and tumor-like lesions. We report that APT-CEST imaging can provide additional information on intracranial brain tumors and tumor-like lesions compared to the information provided by conventional MRI methods, and that it can help indicate the nature of lesions, differentiate between benign and malignant lesions, and determine therapeutic effects. Future research could initiate or improve the lesion-specific clinical applicability of APT-CEST imaging for meningioma embolization, lipoma, leukoencephalopathy, tuberous sclerosis complex, progressive multifocal leukoencephalopathy, and hippocampal sclerosis. Full article

Iron oxide nanoparticles (IONPs) have high relativity for Magnetic Resonance Imaging (MRI) and have shown a long half-life which can covalently bind with drugs and antibodies that can be used for increased contrast while imaging with MRI. IONPs are approved by the U.S Food and Drug Administration to be used as a contrast agent for MRI in vivo. The Cuban Neuroscience Center has developed a new family of naphthalene derivative compounds called Amylovis^® to be used to diagnose and treatment of Alzheimer’s disease (AD). The goal of this work is to synthesize IONPs with different coatings to be conjugated to Amylovis^® as contrast agents for MRI. Coprecipitation method was employed to obtain the magnetic nuclei, and two synthesis methodologies were performed to coat the IONPs (post-synthesis or in situ). The different coatings used were the following: (3-aminopropyl)triethoxysilane (APTES), dicarboxylic polyethyleneglycol, galic acid, polyacrylic acid and citrate. Carbodiimide method was used as synthetic protocol to conjugate the Amylovis^® moiety to different coatings. The nanoparticles were characterized by DRX, FT-IR, Electrophoretic Light Scattering (ELS) and Dynamic Light Scattering (DLS). Moreover, the stability of nanoparticles in water was evaluated using a sedimentation curve. In order to determine the potential interaction of nanosystems with the beta amyloid peptides, a molecular docking was carried out. The theoretical study showed that coatings do not affect the interaction of Amylovis^® with the receptor, and the new polar groups incorporated increased the affinity to receptor. Full article

Vestibular schwannomas are the most common tumor at the common cerebellopontine angle, followed by meningiomas. Differentiation of these tumors is critical because of the different surgical approaches required for treatment. Recent studies have demonstrated the utility of amide proton transfer (APT)-chemical exchange saturation transfer (CEST) imaging in evaluating malignant brain tumors. However, APT imaging has not been applied in benign tumors. Here, we explored the potential of APT in differentiating between schwannomas and meningiomas at the cerebellopontine angle. We retrospectively evaluated nine patients with schwannoma and nine patients with meningioma who underwent APT-CEST MRI from November 2020 to April 2022 pre-operation. All 18 tumors were histologically diagnosed. There was a significant difference in magnetization transfer ratio asymmetry (MTR_asym) values (0.033 ± 0.012 vs. 0.021 ± 0.004; p = 0.007) between the schwannoma and meningioma groups. Receiver operative curve analysis showed that MTR_asym values clearly differentiated between the schwannoma and meningioma groups. At an MTR_asym value threshold of 0.024, the diagnostic sensitivity, specificity, positive predictive value, and negative predictive values for MTR_asym were 88.9%, 77.8%, 80.0%, and 87.5%, respectively. Our results demonstrated the ability of MTR_asym values on APT-CEST imaging to discriminate patients with schwannomas from patients with meningiomas. Full article

As the most common neuro-epithelial tumors of the central nervous system in adults, gliomas are highly malignant and easy to recurrence, with a dismal prognosis. Imaging studies are indispensable for tracking tumor progression (TP) or treatment-related changes (TRCs). During follow-up, distinguishing TRCs from TP in treated patients with gliomas remains challenging as both share similar clinical symptoms and morphological imaging characteristics (with new and/or increasing enhancing mass lesions) and fulfill criteria for progression. Thus, the early identification of TP and TRCs is of great significance for determining the prognosis and treatment. Histopathological biopsy is currently the gold standard for TP and TRC diagnosis. However, the invasive nature of this technique limits its clinical application. Advanced imaging methods (e.g., diffusion magnetic resonance imaging (MRI), perfusion MRI, magnetic resonance spectroscopy (MRS), positron emission tomography (PET), amide proton transfer (APT) and artificial intelligence (AI)) provide a non-invasive and feasible technical means for identifying of TP and TRCs at an early stage, which have recently become research hotspots. This paper reviews the current research on using the abovementioned advanced imaging methods to identify TP and TRCs of gliomas. First, the review focuses on the pathological changes of the two entities to establish a theoretical basis for imaging identification. Then, it elaborates on the application of different imaging techniques and AI in identifying the two entities. Finally, the current challenges and future prospects of these techniques and methods are discussed. Full article

Amide proton transfer (APT)-weighted MRI is a promising molecular imaging technique that has been employed in clinic for detection and grading of brain tumors. MTR_asym, the quantification method of APT, is easily influenced by B₀ inhomogeneity and causes artifacts. Current model-free interpolation methods have enabled moderate B₀ correction for middle offsets, but have performed poorly at limbic offsets. To address this shortcoming, we proposed a practical B₀ correction approach that is suitable under time-limited sparse acquisition scenarios and for B₁ ≥ 1 μT under 3T. In this study, this approach employed a simplified Lorentzian model containing only two pools of symmetric water and asymmetric solutes, to describe the Z-spectral shape with wide and ‘invisible’ CEST peaks. The B₀ correction was then performed on the basis of the fitted two-pool Lorentzian lines, instead of using conventional model-free interpolation. The approach was firstly evaluated on densely sampled Z-spectra data by using the spline interpolation of all acquired 16 offsets as the gold standard. When only six offsets were available for B₀ correction, our method outperformed conventional methods. In particular, the errors at limbic offsets were significantly reduced (n = 8, p < 0.01). Secondly, our method was assessed on the six-offset APT data of nine brain tumor patients. Our MTR_asym (3.5 ppm), using the two-pool model, displayed a similar contrast to the vendor-provided B₀-orrected MTR_asym (3.5 ppm). While the vendor failed in correcting B₀ at 4.3 and 2.7 ppm for a large portion of voxels, our method enabled well differentiation of B₀ artifacts from tumors. In conclusion, the proposed approach could alleviate analysis errors caused by B₀ inhomogeneity, which is useful for facilitating the comprehensive metabolic analysis of brain tumors. Full article