Enhanced Theranostic Efficacy of 89Zr and 177Lu-Labeled Aflibercept in Renal Cancer: A Viable Option for Clinical Practice.

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.

Theranostic role of 89Zr- and 177Lu-labeled aflibercept in breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30-60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC. METHODS: Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin-eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software. RESULTS: FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq. CONCLUSION: 89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC.

FAP expression in adipose tissue macrophages promotes obesity and metabolic inflammation.

Adipose tissue macrophages (ATM) are key players in the development of obesity and associated metabolic inflammation which contributes to systemic metabolic dysfunction. We here found that fibroblast activation protein α (FAP), a well-known marker of cancer-associated fibroblast, is selectively expressed in murine and human ATM among adipose tissue-infiltrating leukocytes. Macrophage FAP deficiency protects mice against diet-induced obesity and proinflammatory macrophage infiltration in obese adipose tissues, thereby alleviating hepatic steatosis and insulin resistance. Mechanistically, FAP specifically mediates monocyte chemokine protein CCL8 expression by ATM, which is further upregulated upon high-fat-diet (HFD) feeding, contributing to the recruitment of monocyte-derived proinflammatory macrophages with no effect on their classical inflammatory activation. CCL8 overexpression restores HFD-induced metabolic phenotypes in the absence of FAP. Moreover, macrophage FAP deficiency enhances energy expenditure and oxygen consumption preceding differential body weight after HFD feeding. Such enhanced energy expenditure is associated with increased levels of norepinephrine (NE) and lipolysis in white adipose tissues, likely due to decreased expression of monoamine oxidase, a NE degradation enzyme, by Fap-/- ATM. Collectively, our study identifies FAP as a previously unrecognized regulator of ATM function contributing to diet-induced obesity and metabolic inflammation and suggests FAP as a potential immunotherapeutic target against metabolic disorders.

Phase patterning of metallic glasses through superfast quenching of ion irradiation-induced thermal spikes.

Amorphous metallic glasses (MGs) convert to crystalline solids upon annealing at a high temperature. Such a phase change, however, does not occur with the local melting caused by damage cascades introduced by ion irradiation, although the resulting thermal spikes can reach temperatures > 1000 K. This is because the quenching rate of the local melting zone is several orders of magnitude higher than the critical cooling rate for MG formation. Thus the amorphous structure is sustained. This mechanism increases the highest temperature at which irradiated MG sustains amorphous phase. More interestingly, if an irradiated MG is pre-annealed to form a polycrystalline structure, ion irradiation can locally convert this crystalline phase to an amorphous phase if the grains are nanometers in size and comparable to the damage cascade volume size. Combining pre-annealing and site selective ion irradiation, patterned crystalline-amorphous heterogeneous structures have been fabricated. This finding opens new doors for various applications.

Qualitative and quantitative analysis of four benzimidazole residues in food by surface-enhanced Raman spectroscopy combined with chemometrics.

In this study, surface-enhanced Raman spectroscopy (SERS) combined with chemometric methods were developed for qualitative and quantitative analysis of four benzimidazole (BMZs) residues in corn. Sulfhydryl functionalized Fe3O4@SiO2@Ag-SH magnetic SERS substrates were prepared to obtain the SERS spectra of four BMZs for chemometric analysis. The partial least squares regression discrimination analysis (PLS-DA) model performed best, with a recall rate upwards 99.17%, and could successfully distinguish four BMZs. Under the support vector machine regression (SVR) model, the detection limits of carbendazim, benomyl, thiophanate-methyl and thiabendazole were 0.055 mg/L, 0.056 mg/L, 0.067 mg/L and 0.093 mg/L, respectively; the average recovery was in the range of 85.6%-107.5%. Furthermore, the method verified by HPLC, and the results showed that there was no significant difference between two methods (p > 0.05). Therefore, the strategy based on SERS coupling chemometrics can be served as a promising tool for rapid determination of BMZs residues in food.

Prediction of Stroke Onset Time With Combined Fast High-Resolution Magnetic Resonance Spectroscopic and Quantitative T2 Mapping.

OBJECTIVE: The purpose of this work is to develop a multispectral imaging approach that combines fast high-resolution 3D magnetic resonance spectroscopic imaging (MRSI) and fast quantitative T2 mapping to capture the multifactorial biochemical changes within stroke lesions and evaluate its potentials for stroke onset time prediction. METHODS: Special imaging sequences combining fast trajectories and sparse sampling were used to obtain whole-brain maps of both neurometabolites (2.0 × 3.0 × 3.0 mm3) and quantitative T2 values (1.9 × 1.9 × 3.0 mm3) within a 9-minute scan. Participants with ischemic stroke at hyperacute (0-24 h, n = 23) or acute (24 h-7d, n = 33) phase were recruited in this study. Lesion N-acetylaspartate (NAA), lactate, choline, creatine, and T2 signals were compared between groups and correlated with patient symptomatic duration. Bayesian regression analyses were employed to compare the predictive models of symptomatic duration using multispectral signals. RESULTS: In both groups, increased T2 and lactate levels, as well as decreased NAA and choline levels were detected within the lesion (all p < 0.001). Changes in T2, NAA, choline, and creatine signals were correlated with symptomatic duration for all patients (all p < 0.005). Predictive models of stroke onset time combining signals from MRSI and T2 mapping achieved the best performance (hyperacute: R2 = 0.438; all: R2 = 0.548). CONCLUSION: The proposed multispectral imaging approach provides a combination of biomarkers that index early pathological changes after stroke in a clinical-feasible time and improves the assessment of the duration of cerebral infarction. SIGNIFICANCE: Developing accurate and efficient neuroimaging techniques to provide sensitive biomarkers for prediction of stroke onset time is of great importance for maximizing the proportion of patients eligible for therapeutic intervention. The proposed method provides a clinically feasible tool for the assessment of symptom onset time post ischemic stroke, which will help guide time-sensitive clinical management.

Predicting the Onset of Ischemic Stroke With Fast High-Resolution 3D MR Spectroscopic Imaging.

BACKGROUND: Neurometabolite concentrations provide a direct index of infarction progression in stroke. However, their relationship with stroke onset time remains unclear. PURPOSE: To assess the temporal dynamics of N-acetylaspartate (NAA), creatine, choline, and lactate and estimate their value in predicting early (<6 hours) vs. late (6-24 hours) hyperacute stroke groups. STUDY TYPE: Cross-sectional cohort. POPULATION: A total of 73 ischemic stroke patients scanned at 1.8-302.5 hours after symptom onset, including 25 patients with follow-up scans. FIELD STRENGTH/SEQUENCE: A 3 T/magnetization-prepared rapid acquisition gradient echo sequence for anatomical imaging, diffusion-weighted imaging and fluid-attenuated inversion recovery imaging for lesion delineation, and 3D MR spectroscopic imaging (MRSI) for neurometabolic mapping. ASSESSMENT: Patients were divided into hyperacute (0-24 hours), acute (24 hours to 1 week), and subacute (1-2 weeks) groups, and into early (<6 hours) and late (6-24 hours) hyperacute groups. Bayesian logistic regression was used to compare classification performance between early and late hyperacute groups by using different combinations of neurometabolites as inputs. STATISTICAL TESTS: Linear mixed effects modeling was applied for group-wise comparisons between NAA, creatine, choline, and lactate. Pearson's correlation analysis was used for neurometabolites vs. time. P < 0.05 was considered statistically significant. RESULTS: Lesional NAA and creatine were significantly lower in subacute than in acute stroke. The main effects of time were shown on NAA (F = 14.321) and creatine (F = 12.261). NAA was significantly lower in late than early hyperacute patients, and was inversely related to time from symptom onset across both groups (r = -0.440). The decrease of NAA and increase of lactate were correlated with lesion volume (NAA: r = -0.472; lactate: r = 0.366) in hyperacute stroke. Discrimination was improved by combining NAA, creatine, and choline signals (area under the curve [AUC] = 0.90). DATA CONCLUSION: High-resolution 3D MRSI effectively assessed the neurometabolite changes and discriminated early and late hyperacute stroke lesions. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Simultaneous Mapping of Water Diffusion Coefficients and Metabolite Distributions of the Brain Using MR Spectroscopic Imaging Without Water Suppression.

OBJECTIVE: To simultaneously map water diffusion coefficients and metabolite distributions of the brain in magnetic resonance spectroscopic imaging (MRSI) experiments within a clinically feasible time. METHODS: A diffusion-preparation module was introduced in water-unsuppressed MRSI acquisition sequence to generate diffusion weighting of the water signals. Fast spatiospectral encodings were achieved using echo-planar spectroscopic imaging readouts with blipped phase encodings for sparse sampling. Navigator signals were embedded in the data acquisition sequence, which were used for detection of data corrupted by physiological motion in the diffusion preparation period. In data processing, a novel model-based method was developed to effectively use sparse (k, t)-space spectroscopic signals for reconstruction of the spatial distributions of water diffusion coefficients and metabolite concentrations. RESULTS: Both phantom experiments and in vivo experiments were carried out to evaluate the feasibility and performance of the proposed method. In an 8-minute scan, diffusion weighted images and apparent diffusion coefficients map at 2.0×1.0×1.0 mm3 were obtained simultaneously with metabolite maps at 2.0×3.0×3.0 mm3 nominal resolution. CONCLUSION: We demonstrated the feasibility of using the unsuppressed water signals from MRSI experiments to map the water diffusion coefficients of brain tissues and proposed a novel method to achieve simultaneous mapping of water diffusion coefficients and metabolite distributions. SIGNIFICANCE: The proposed method provides a unique imaging tool for simultaneous diffusion and metabolic imaging. This method is expected to be useful for various brain imaging applications.

Circulating Tumor Cells and Breast Cancer Metastasis: From Enumeration to Somatic Mutational Profile.

Aims: This study investigates the association between circulating tumor cells (CTCs) and breast cancer metastasis. Methods: A retrospective study was conducted using patients with histologically confirmed breast cancer recruited from the First Affiliated Hospital of Nanjing Medical University during the period of August 2017−October 2020. We used adjusted logistic regression, the random forest algorithm, and sensitivity analysis to study the association between CTC enumeration and tumor metastasis. Further, we performed next-generation sequencing (NGS) on the CTCs obtained from two patients with breast cancer brain metastasis. Results: A total of 41 out of 116 enrolled patients were identified with tumor metastasis. CTC enumeration was significantly higher in patients with liver metastasis than in those without liver metastasis. Patients with CTCs ≥ 5 exhibited a higher risk of tumor metastasis than those with CTCs < 5 in the adjusted model (odds ratios (OR) = 6.25, 95% confidence interval (CI) = 2.63−15.58). The random forest model identified CTC enumeration as a significant metastasis-related variable with the highest mean decrease accuracy and mean decrease Gini score. No significant association was found between CTCs and visceral metastasis with an OR of 1.29 (95% CI = 0.98−2.05, p = 0.232). Upon further investigating organ-specific metastasis, we found that patients with high CTC levels were more likely to develop liver metastasis (OR = 4.87, 95% CI = 1.34−20.17, p = 0.021). The NGS study of CTCs identified a total of 120 indel mutations (e.g., CNGB1, NTSR1, ZG16). The enriched biological processes were mechanoreceptor differentiation and macrophage activation involved in the immune response. The enriched KEGG pathways included focal adhesion, the PI3K-Akt signaling pathway, and microRNAs involved in cancer. Conclusions: Our study revealed that CTCs ≥ 5 are a risk factor for tumor metastasis in breast cancer patients. In addition, we reported that CTCs ≥ 5 might be associated with a higher risk of liver metastasis in patients with metastatic breast cancer. We have provided the mutational profiles of CTCs based on next-generation sequencing.

The Degree of Plasma Oxidized Low-Density Lipoprotein Level Decrease Is Related to Clinical Outcomes for Patients with Acute Ischemic Stroke.

OBJECTIVE: To investigate the relationship between the decrease of plasma oxidized low-density lipoprotein (oxLDL) levels and clinical outcomes in patients with acute atherosclerosis-related ischemic stroke. METHODS: We recruited acute ischemic stroke patients within 3 days of onset consecutively. Plasma oxLDL levels were measured on the second day after admission and before discharge (10-14 days after stroke onset). Initial stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) scores, and infarct volume was measured using diffusion-weighted imaging (DWI) by the ITK-SNAP software. Clinical outcomes were evaluated by DWI volumes in the acute phase, neurological improvement at discharge, and favorable functional prognosis at 90 days. Logistic regression was performed to evaluate the association between oxLDL level decrease and clinical outcomes. RESULTS: 207 patients were enrolled in this study. Compared with the mild decrease of the oxLDL level group, patients with a significant decrease of the oxLDL level group were more likely to have a higher ratio of neurological improvement at discharge (55.07% vs. 14.49%, p < 0.01) and favorable functional prognosis at 90 days (91.30% vs. 55.07%, p < 0.01). In multivariable logistic regression, the degree of oxLDL level decrease was related to neurological improvement at discharge and favorable functional prognosis at 90 days (p < 0.01). Patients with significant decrease were more likely to have neurological improvement at discharge (OR = 7.92, 95% CI, 3.14-19.98, and p < 0.01) and favorable functional prognosis at 90 days (OR = 7.46, 95% CI, 2.40-23.23, and p < 0.01) compared to patients with mild decrease of oxLDL level. The DWI volumes in patients with different oxLDL level decrease groups had no statistical difference (p = 0.41), and the Spearman's rho between oxLDL level decrease and DWI infarct volumes was -0.03, but no statistical difference (p = 0.72). CONCLUSIONS: The degree of oxLDL level decrease is related to neurological improvement at discharge and favorable functional prognosis at 90 days for patients with acute atherosclerosis-related ischemic stroke, but not with infarct volume in the acute phase.

High-Resolution Label-Free Molecular Imaging of Brain Tumor.

Molecular imaging has long been recognized as an important tool for diagnosis, characterization, and monitoring of treatment responses of brain tumors. Magnetic resonance spectroscopic imaging (MRSI) is a label-free molecular imaging technique capable of mapping metabolite distributions non-invasively. Several metabolites detectable by MRSI, including Choline, Lactate and N-Acetyl Aspartate, have been proved useful biomarkers for brain tumor characterization. However, clinical application of MRSI has been limited by poor resolution, small spatial coverage, low signal-to-noise ratio and long scan time. This work presents a novel MRSI method for fast, high-resolution metabolic imaging of brain tumor. This method synergistically integrates fast acquisition sequence, sparse sampling, subspace modeling and machine learning to enable 3D mapping of brain metabolites with a spatial resolution of 2.0×3.0×3.0 mm3 in a 7-minute scan. Experimental results obtained from patients with diagnosed brain tumor showed great promise for capturing small-size tumors and revealing intra-tumor metabolic heterogeneities.Clinical Relevance - This paper presents a novel technique for label-free molecular imaging of brain tumor. With further development, this technology may enable many potential clinical applications, from tumor detection, characterization, to assessment of treatment efficacy.

Reduced Cerebral Blood Flow in Benign Oligemia Relates to Poor Clinical Outcome in Acute Ischemic Stroke Patients.

The imaging of cerebral blow flow (CBF) has shown great promise in predicting the tissue outcome or functional outcome of acute ischemic stroke patients. Arterial spin labeling (ASL) provides a noninvasive tool for quantitative CBF measurement and does not require a contrast agent, which makes it an attractive technology for perfusion imaging in clinical settings. Previous studies have shown the feasibility of using ASL for acute stroke imaging and its potential in stroke outcome prediction. However, the relationship between the tissue-level CBF reduction in hypoperfused region and clinical outcome in acute stroke patients remains not well understood. In this study, we obtained the quantitative measurements of CBF in acute ischemic stroke patients (N = 18) using pseudocontinuous ASL (pCASL) perfusion imaging technology. The tissue-level CBF changes were evaluated and their correlations with patient clinical outcome were explored. Our results showed different CBF values between hypoperfused tissues recruited into infarction and those that survived. Moreover, a significant correlation was found specifically between the CBF reduction in benign oligemia area and patient neurological deficit severity. These findings showed the validity of pCASL perfusion imaging in the assessment of tissue-level CBF information in acute stroke. The association of CBF with patient clinical outcome might provide useful insights in early diagnosis of acute stroke patients.

Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Level is Related to Clinical Prognosis In Patients with Acute Atherosclerosis-related Ischemic Stroke.

To investigate the associations between soluble Lectin-like Oxidized Low-density lipoprotein receptor-1 (sLOX-1) and clinical prognosis, especially infarct volume in patients with acute atherosclerosis-related ischemic stroke. We recruited acute ischemic stroke patients within 3 days after onset. Patients were stratified into 3 groups by sLOX-1 level. Initial stroke severity was assessed using the National Institutes of Health Stroke Scale scores, and infarct volume was measured using DWI by ITK-SNAP software. The clinical prognosis was evaluated by DWI volume, clinical response at discharge, and functional outcome at 90 days. Spearman rank correlation analysis was used to examine associations between circulating sLOX-1 levels and infarct volumes. Logistic regression was used to explore the relationship between sLOX-1 levels and clinical prognosis. A total of 207 patients were included in our study. The median DWI volume in the lowest sLOX-1 tertile was 1.98 cm3, smaller than 4.26 cm3 in the highest sLOX-1 group. The Spearman rank correlation coefficient between sLOX-1 levels and DWI volume was 0.47 (P < .01). Compared with the highest sLOX-1 tertiles, patients in the lowest sLOX-1 tertile had a higher risk of favorable functional outcome at 90 days (OR = 3.47, 95% CI, 1.21-9.96) after adjusting traditional risk factors. However, there was no difference between sLOX-1 level and clinical response at discharge. For patients with acute atherosclerosis-related ischemic stroke, circulating sLOX-1 level is correlated with DWI volume in the acute phase and favorable functional outcome at 90 days, but not with the clinical response at discharge.

Arcuate Fasciculus Subsegment Impairments Distinctly Associated with Memory and Language Deficits in Acute Mild Traumatic Brain Injury Patients.

In acute mild traumatic brain injury (mTBI), the injury-related axonal swelling leads to white matter fiber bundle impairments, closely related to the memory and language deficits commonly shown in the patients. The arcuate fasciculus (AF) plays a central role in verbal learning and language function but could be functionally heterogeneous along the fiber tract. In this study, 25 patients with acute mTBI (<48 h after trauma) and 33 age- and sex-matched healthy controls (HCs) were included. Impaired verbal memory and language functions were shown in the patient group compared with the HCs. Combined diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) were applied to investigate the altered diffusion measure profiles of the AF tracts and the associated functional features. The fractional anisotropy (FA) in the right AF temporal subsegment of the mTBI group was negatively associated with the patient verbal memory function, whereas a positive correlation was found in the HC group. On the other hand, the correlation between the FA in the right AF frontal subsegment and the language function in HCs diminished in the patient group. Moreover, the functional connectivity between the inferior frontal gyrus and the middle occipital gyrus decreased, and its correlation with language function in HCs was absent in the patients with mTBI. Our work provides new insights into the understanding of the structural and functional heterogeneity of the AF tracts as well as the distinct associations of its subsegment impairments with verbal memory and language function deficits in patients with acute mTBI.

Accelerating T2 mapping of the brain by integrating deep learning priors with low-rank and sparse modeling.

PURPOSE: To accelerate T2 mapping with highly sparse sampling by integrating deep learning image priors with low-rank and sparse modeling. METHODS: The proposed method achieves high-speed T2 mapping by highly sparsely sampling (k, TE)-space. Image reconstruction from the undersampled data was done by exploiting the low-rank structure and sparsity in the T2 -weighted image sequence and image priors learned from training data. The image priors for a single TE were generated from the public Human Connectome Project data using a tissue-based deep learning method; the image priors were then transferred to other TEs using a generalized series-based method. With these image priors, the proposed reconstruction method used a low-rank model and a sparse model to capture subject-dependent novel features. RESULTS: The proposed method was evaluated using experimental data obtained from both healthy subjects and tumor patients using a turbo spin-echo sequence. High-quality T2 maps at the resolution of 0.9 × 0.9 × 3.0 mm3 were obtained successfully from highly undersampled data with an acceleration factor of 8. Compared with the existing compressed sensing-based methods, the proposed method produced significantly reduced reconstruction errors. Compared with the deep learning-based methods, the proposed method recovered novel features better. CONCLUSION: This paper demonstrates the feasibility of learning T2 -weighted image priors for multiple TEs using tissue-based deep learning and generalized series-based learning. A new method was proposed to effectively integrate these image priors with low-rank and sparse modeling to reconstruct high-quality images from highly undersampled data. The proposed method will supplement other acquisition-based methods to achieve high-speed T2 mapping.

Simultaneous QSM and metabolic imaging of the brain using SPICE: Further improvements in data acquisition and processing.

PURPOSE: To achieve high-resolution mapping of brain tissue susceptibility in simultaneous QSM and metabolic imaging. METHODS: Simultaneous QSM and metabolic imaging was first achieved using SPICE (spectroscopic imaging by exploiting spatiospectral correlation), but the QSM maps thus obtained were at relatively low-resolution (2.0 × 3.0 × 3.0 mm3 ). We overcome this limitation using an improved SPICE data acquisition method with the following novel features: 1) sampling (k, t)-space in dual densities, 2) sampling central k-space fully to achieve nominal spatial resolution of 3.0 × 3.0 × 3.0 mm3 for metabolic imaging, and 3) sampling outer k-space sparsely to achieve spatial resolution of 1.0 × 1.0 × 1.9 mm3 for QSM. To keep the scan time short, we acquired spatiospectral encodings in echo-planar spectroscopic imaging trajectories in central k-space but in CAIPIRINHA (controlled aliasing in parallel imaging results in higher acceleration) trajectories in outer k-space using blipped phase encodings. For data processing and image reconstruction, a union-of-subspaces model was used, effectively incorporating sensitivity encoding, spatial priors, and spectral priors of individual molecules. RESULTS: In vivo experiments were carried out to evaluate the feasibility and potential of the proposed method. In a 6-min scan, QSM maps at 1.0 × 1.0 × 1.9 mm3 resolution and metabolic maps at 3.0 × 3.0 × 3.0 mm3 nominal resolution were obtained simultaneously. Compared with the original method, the QSM maps obtained using the new method reveal fine-scale brain structures more clearly. CONCLUSION: We demonstrated the feasibility of achieving high-resolution QSM simultaneously with metabolic imaging using a modified SPICE acquisition method. The improved capability of SPICE may further enhance its practical utility in brain mapping.

Fast high-resolution metabolic imaging of acute stroke with 3D magnetic resonance spectroscopy.

Impaired oxygen and cellular metabolism is a hallmark of ischaemic injury in acute stroke. Magnetic resonance spectroscopic imaging (MRSI) has long been recognized as a potentially powerful tool for non-invasive metabolic imaging. Nonetheless, long acquisition time, poor spatial resolution, and narrow coverage have limited its clinical application. Here we investigated the feasibility and potential clinical utility of rapid, high spatial resolution, near whole-brain 3D metabolic imaging based on a novel MRSI technology. In an 8-min scan, we simultaneously obtained 3D maps of N-acetylaspartate and lactate at a nominal spatial resolution of 2.0 × 3.0 × 3.0 mm3 with near whole-brain coverage from a cohort of 18 patients with acute ischaemic stroke. Serial structural and perfusion MRI was used to define detailed spatial maps of tissue-level outcomes against which high-resolution metabolic changes were evaluated. Within hypoperfused tissue, the lactate signal was higher in areas that ultimately infarcted compared with those that recovered (P < 0.0001). Both lactate (P < 0.0001) and N-acetylaspartate (P < 0.001) differed between infarcted and other regions. Within the areas of diffusion-weighted abnormality, lactate was lower where recovery was observed compared with elsewhere (P < 0.001). This feasibility study supports further investigation of fast high-resolution MRSI in acute stroke.

Correlation between White Matter Hyperintensities Related Gray Matter Volume and Cognition in Cerebral Small Vessel Disease.

BACKGROUND AND AIM: The relationship between severity of cerebral small vessel disease, as defined by white matter hyperintensities classification, and gray matter volume of different brain regions has not been well defined. This study aimed to investigate brain regions with significant differences in gray matter volume associated with different degrees of white matter hyperintensities in patients with cerebral small vessel disease. Meanwhile, we examined whether correlations existed between gray matter volume in different brain regions and cognitive ability. METHODS: 110 cerebral small vessel disease patients underwent 3.0T Magnetic resonance imaging scans and neuropsychological cognitive assessments. White matter hyperintensities of each subject was graded according to Fazekas grade scale and was divided into two groups: (A) White matter hyperintensities score of 1-2 points (n = 64), (B) White matter hyperintensities score of 3-6 points (n = 46). Gray matter volume was analyzed using voxel-based morphometry implemented in Statistical Parametric Mapping 12 software. RESULTS: Brain regions with significant differences in gray matter volume between groups were diffused throughout the brain. Patients with high white matter hyperintensities scores exhibited decreased gray matter volume in some subregions of the frontal lobes, the temporal lobes, the parahippocampal gyrus, hippocampus and thalamus (p < 0.05). Among them, gray matter volume in the ventrolateral area of right inferior temporal gyrus, together with the right posterior parietal and occipital thalamus were positively correlated with Montreal Cognitive Assessment scores (p < 0.05). Gray matter volume in the extreme ventrolateral area of right inferior temporal gyrus along with the entorhinal cortex of left parahippocampal gyrus were positively correlated with both Montreal Cognitive Assessment and Mini-Mental Status Examination scores (p < 0.05). CONCLUSIONS: Cerebral small vessel disease is considered as a whole brain disease and local white matter lesions can influence the gray matter in remote areas. Reducing the severity and progression of white matter hyperintensities may help to prevent secondary brain atrophy and cognitive impairment.

A machine learning approach for magnetic resonance image-based mouse brain modeling and fast computation in controlled cortical impact.

Computational modeling of the brain is crucial for the study of traumatic brain injury. An anatomically accurate model with refined details could provide the most accurate computational results. However, computational models with fine mesh details could take prolonged computation time that impedes the clinical translation of the models. Therefore, a way to construct a model with low computational cost while maintaining a computational accuracy comparable with that of the high-fidelity model is desired. In this study, we constructed magnetic resonance (MR) image-based finite element (FE) models of a mouse brain for simulations of controlled cortical impact. The anatomical details were kept by mapping each image voxel to a corresponding FE mesh element. We constructed a super-resolution neural network that could produce computational results of a refined FE model with a mesh size of 70 µm from a coarse FE model with a mesh size of 280 µm. The peak signal-to-noise ratio of the reconstructed results was 33.26 dB, while the computational speed was increased by 50-fold. This proof-of-concept study showed that using machine learning techniques, MR image-based computational modeling could be applied and evaluated in a timely fashion. This paved ways for fast FE modeling and computation based on MR images. Results also support the potential clinical applications of MR image-based computational modeling of the human brain in a variety of scenarios such as brain impact and intervention.Graphical abstract MR image-based FE models with different mesh sizes were generated for CCI. The training and testing data sets were computed with 5 different impact locations and 3 different impact velocities. High-resolution strain maps were estimated using a SR neural network with greatly reduced computational cost.