Search

Implanted vagus nerve stimulation (VNS) and transcutaneous auricular VNS (taVNS) have been primarily administered clinically to the unilateral-left vagus nerve. This left-only convention has proved clinically beneficial in brain disorders. However, in stroke survivors, the presence of a lesion in the brain may complicate VNS-mediated signaling, and it is important to understand the laterality effects of VNS in stroke survivors to optimize the intervention. To understand whether taVNS delivered to different ear targets relative to the lesion (ipsilesional vs contralesional vs bilateral vs sham) impacts blood oxygenation level dependent (BOLD) signal propagation in stroke survivors. We enrolled 20 adults with a prior history of stroke. Each participant underwent a single visit, during which taVNS was delivered concurrently during functional magnetic resonance imaging (fMRI) acquisition. Each participant received three discrete active stimulation conditions (ipsilesional, contralesional, bilateral) and one sham condition in a randomized order. Stimulation-related BOLD signal changes in the active conditions were compared to sham conditions to understand the interaction taVNS and laterality effects. All active taVNS conditions deactivated the contralesional default mode network related regions compared to sham, however only ipsilesional taVNS enhanced the activations in the ipsilesional visuomotor and secondary visual cortex. Furthermore, we reveal an interaction in task activations between taVNS and cortical visuomotor areas, where ipsilesional taVNS significantly increased ipsilesional visuomotor activity and decreased contralesional visuomotor activity compared to sham. Laterality of taVNS relative to the lesion is a critical factor in optimizing taVNS in a stroke population, with ipsilesional stimulation providing largest direct brain activation and should be explored further when designing taVNS studies in neurorehabilitation. • Concurrent taVNS/fMRI can help better understand and optimize ear stimulation targets. • TaVNS engages motor recovery related brain regions in stroke, with discrete laterality effects. • Ipsilesional taVNS induces the most robust brain activations in a stroke population. • TaVNS ear target relative to the lesion in stroke patients is an important consideration. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The direct damage caused by ischemic stroke is relatively localized, but structural reorganization of cortical regions could occur across the brain. Changes of large-scale, cortical structural brain networks after basal ganglia stroke are less well reported. We, therefore, aim to explore the abnormalities of cortical morphology and structural network topology in patients with unilateral basal ganglia stroke during the subacute period.Materials and Methods: Thirty patients with first-ever basal ganglia stroke and thirty age- and sex-matched healthy controls were recruited for our analysis. Patients underwent structural magnetic resonance imaging examinations and clinical assessment from seven days to three months post-stroke. Alterations in cortical morphology and topological properties of the cortical structural network were measured respectively using the surface-based morphology and graph-theoretical methods.Results: We observed focal cortical atrophy, specifically in areas of frontal and temporal cortices. Moreover, the cortical thickness in the contralesional transverse temporal gyrus and superior temporal gyrus was positively correlated with cognitive function scores. Network analysis revealed that patients with basal ganglia stroke showed increased clustering coefficient, increased mean local efficiency as well as a reorganization of degree-based hubs. In addition, these patients also showed reduced robustness under a random attack compared to healthy controls.Conclusion: These findings indicated a unique pattern of cortical reorganization and the abnormal topological organization of cortical thickness-based structural covariance networks in patients with basal ganglia stroke, which is beneficial to understand the pathophysiological mechanisms of functional disorders at the cortical structural network level and find potential targets for induced neuromodulation. [ABSTRACT FROM AUTHOR]

Bioadhesives such as tissue adhesives, hemostatic agents, and tissue sealants have gained increasing popularity in different areas of clinical operations during the last three decades. Bioadhesives can be categorized into internal and external ones according to their application conditions. External bioadhesives are generally applied in topical medications such as wound closure and epidermal grafting. Internal bioadhesives are mainly used in intracorporal conditions with direct contact to internal environment including tissues, organs and body fluids, such as chronic organ leak repair and bleeding complication reduction. This review focuses on internal bioadhesives that, in contrast with external bioadhesives, emphasize much more on biocompatibility and adhesive ability to wet surfaces rather than on gluing time and intensity. The crosslinking mechanisms of present internal bioadhesives can be generally classified as follows: 1) chemical conjugation between reactive groups; 2) free radical polymerization by light or redox initiation; 3) biological or biochemical coupling with specificity; and 4) biomimetic adhesion inspired from natural phenomena. In this review, bioadhesive products of each class are summarized and discussed by comparing their designs, features, and applications as well as their prospects for future development. Statement of Significance Despite the emergence of numerous novel bioadhesive formulations in recent years, thus far, the classification of internal and external bioadhesives has not been well defined and universally acknowledged. Many of the formulations have been proposed for treatment of several diseases even though they are not applicable for such conditions. This is because of the lack of a systematic standard or evaluation protocol during the development of a new adhesive product. In this review, the definition of internal and external bioadhesives is given for the first time, and with a focus on internal bioadhesives, the criteria of an ideal internal bioadhesive are adequately discussed; this is followed by the review of recently developed internal bioadhesives based on different gluing mechanisms. [ABSTRACT FROM AUTHOR]

To date, existing tissue adhesives have various weak points in gluing kinetics and stability – particularly, in biocompatibility, which make most of them remain suboptimal for internal conditions. Herein, a novel mussel-inspired “BCD” tissue glue made of bovine serum albumin (BSA), citrate acid (CA) and dopamine was developed aiming at internal medical applications. BSA was employed as a natural and biocompatible macromolecular backbone; CA was introduced as a dual-functional intermediate to increase reactive carboxyl sites for engraftment of dopamine onto BSA backbone and also block the competing reactive amines from the proteinic backbone. Timely curing and stable adhesion were achieved between biological tissue substrates via instant chelation and gradual conjugation of DOPA-catechol groups in BCD glue. Within 30 min, this newly developed BCD tissue glue can provide over 10-fold greater adhesion stress than that of commercially available fibrin glue in wet environment. As a tissue adhesive for internal use, its superior properties also include ideal gelation kinetics and swelling behaviour, appropriate degradation rate, sound cytocompatibility in vitro, as well as fine biocompatibility in vivo. More importantly, successful animal experimentations in seroma prevention and instant hemostasis ultimately validated BCD tissue glue's preclinical efficacy as a tissue adhesive for various internal medical applications. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to use DKI to detect the microstructural change of the discs in matured normal rats. Methods Total 24 normal SD rats (12 males/12 females) underwent DWI/DKI and T2 sequences with a 3T MRI scanner to get the values of ADC, FA, MD, Da, Dr, MK, Ka and Kr. The discs were categorized using a five-grade degeneration grading system in the T2-images. The height of the discs and the parameters in DWI/DKI were measured to compare between the different grades and sexes. The histological images and the images of fiber tracking were also done in the discs. Results There were 30 Grade 1 and 18 Grade 2 in the discs. Compared with Grade 1, decreased ADC, increased FA and MK values were observed in Grade 2 (P < 0.05). By the ROC analysis of grades of the discs, there was low diagnostic accuracy in ADC value, while FA and MK showed higher accuracy. In Grade 1, there were lower ADC value, lower Dr, higher MK, Ka and Kr in male's group than them in female's group. There were no differences in the parameters except the ADC value in the two sexes in Grade 2. The different microstructure of the normal discs in the male and female rats had been proved by the histological images and the images of fiber tracking. Conclusion DKI is a noninvasive and sustainable means to test the changes of intervertebral discs. The discs in Grade 2 were also found in the normal matured SD rat tails. The assessment of the grade of the discs in T2-images should be done before the experimental management. There was microstructural difference in the nucleus pulposus in the discs in Grade 1 and 2. FA and MK showed higher diagnostic accuracy. The laboratory rats should be the same sex because the microstructure of the normal discs weren't the same. [ABSTRACT FROM AUTHOR]

It has been a great challenge to develop aldehyde-free tissue adhesives that can function rapidly and controllably on wet internal tissues with fine adhesion strength, sound biocompatibility and degradability. To this end, we have devised a mussel-inspired easy-to-use double-crosslink tissue adhesive (DCTA) comprising a dopamine-conjugated gelatin macromer, a rapid crosslinker (namely, Fe 3+ ), and a long-term acting crosslinker (namely, genipin). As a mussel-inspired gluing macromer, dopamine is grafted onto gelatin backbone via an one-step reaction, the catechol groups of which are capable of performing strong wet adhesion on tissue surfaces. By addition of genipin and Fe 3+ , the formation of catechol–Fe 3+ complexation and accompanying spontaneous curing of genipin-primed covalent crosslinking of gluing macromers in one pot endows DCTA with the double-crosslink adhesion mechanism. Namely, the reversible catechol–Fe 3+ crosslinking executes an controllable and instant adhesive curing; while genipin-induced stable covalent crosslinking promises it with long-term effectiveness. This novel DCTA exhibits significantly higher wet tissue adhesion capability than the commercially available fibrin glue when applied on wet porcine skin and cartilage. In addition, this DCTA also demonstrates fine elasticity, sound biodegradability, and biocompatibility when contacting in vitro cultured cells and blood. In vivo biocompatibility and biodegradability are checked and confirmed via trials of subcutaneous implantation in nude mice model. This newly developed DCTA may be a highly promising product as a biological glue for internal medical use including internal tissue adhesion, sealing, and hemostasis. Statement of Significance There is a great demand for ideal tissue adhesives that can be widely used in gluing wet internal tissues. Here, we have devised a mussel-inspired easy-to-use double-crosslink tissue adhesive (DCTA) that meets the conditions as an ideal tissue adhesive. It is composed of gelatin–dopamine conjugates – a gluing macromer, Fe 3+ – a rapid crosslinker, and genipin – a long-term acting crosslinker. This DCTA is constructed with a novel complexation-covalent double-crosslinking principle in one pot, in which the catechol–Fe 3+ crosslinking executes a controllable and instant adhesive curing, at the same time, genipin-induced covalent crosslinking promises it with long-term effectiveness in physiology conditions. This novel DCTA, with excellent wet tissue adhesion capability, fine elasticity, sound biodegradability, and biocompatibility, is a promising biological glue for internal medical use in surgical operations. [ABSTRACT FROM AUTHOR]

It is difficult to predict the neurologic outcome of neonates with hypoxic-ischemic encephalopathy (HIE). Our goal was to investigate the prognostic values of magnetic resonance spectroscopy (MRS) in neonatal HIE. During this study, 46 neonates with HIE underwent magnetic resonance imaging (MRI) and proton MRS (1HMRS). The sample included 25 cases of mild HIE, 11 cases of moderate HIE, and 10 cases of severe HIE. Nine healthy neonates without asphyxia served as controls. 1HMRS techniques included single-voxel MRS and 2-D–point-resolved spatially localized spectroscopy (PRESS) multivoxel chemical shift spectroscopy imaging. Then, 31 of 46 neonates with HIE were divided into 3 groups according to their prognosis: dead, abnormal, and normal outcome. Abnormal and normal outcome were defined by follow-up MRI. Metabolic changes were analyzed and compared with HIE grading and prognosis. As a result, the ▪ GLx-α peak was markedly increased in the moderate and severe HIE groups. The GLx-α/Cr ratio in the control, mild, moderate, and severe HIE groups was 0.18, 0.21, 0.64, 1.31, respectively. The Lac/Cr ratio was 0.12, 0.14, 0.19, and 0.26, respectively. A Spearman rank correlation test confirmed that the ratio of GLx-α/Cr and Lac/Cr had significant positive correlation with clinical grading of HIE (P < 0.01). The ▪ GLx-α/Cr ratio in the dead, abnormal, and normal outcome groups was 1.28, 0.82, and 0.25, respectively; the Lac/Cr ratio was 0.34, 0.19, and 0.14, respectively. An anaylsis of variance demonstrated that the differences were significant (both P < 0.01). A ▪ Spearman rank correlation test confirmed that the ratio of GLx-α/Cr and Lac/Cr had significant negative correlation with prognosis of HIE; GLx-α/Cr showed a much stronger correlation than the Lac/Cr ratio (P < 0.01). ▪ The formula of the relationship between the poor prognosis of HIE and the ratio of GLx-α/Cr in basal ganglia was established by the logistic regression model. In conclusion, 1HMRS is a useful tool for evaluating the severity and prognosis of HIE. The higher ratio of GLx-α/Cr in the basal ganglia and thalamus may predict a poor outcome in neonates with HIE. [Copyright &y& Elsevier]

• MUSE-DTI acquired a better image quality compared to traditional DTI. • MUSE-DTI parameters of the spinal cord at MCL in CSM patients were significantly grade-dependent and all correlated with clinical JOA scores. • The AD C2 values can reflect the secondary damage of distal spinal cord. The most frequent type of spinal cord injury is cervical spondylotic myelopathy (CSM). Conventional structural magnetic resonance imaging (MRI) is the gold diagnosis standard for CSM. Diffusion tensor imaging (DTI) could reflect microstructural changes in the spinal cord by tracing water molecular diffusion in early stages of CSM. However, due to the complex local anatomical structure and small field of view of the spinal cord, the imaging effect of traditional DTI imaging on the spinal cord is limited. MUSE (MUltiplexed Sensitivity-Encoding) -DTI is a novel diffusion-weighted imaging (DWI) sequence that achieves higher signal intensity through multiple excitation acquisition. MUSE sequence may improve the quality of spinal cord DTI imaging. Prospective study. This study aimed to investigate the clinical diagnosis value of a novel protocol of MUSE-DTI in patients with cervical spondylotic myelopathy (CSM). From August 2021 to March 2022, a total of 60 subjects (22–71 years) were enrolled, including 51 CSM patients (22 males, 29 females) and 9 healthy subjects (4 males and 5 females). Each subject underwent a MUSE-DTI examination and a clinical Japanese Orthopedic Association (JOA) scale. We measured values of FA (Fractional Anisotropy), MD (Mean Diffusivity), AD (Axial Diffusivity), and RD (Radial Diffusivity), and collected the clinical JOA scores of each subject before the MR examination. A 3.0T MR scanner (Signa Architect, GE Healthcare) performed the MUSE-DTI sequence on each subject. The cervical canal stenosis of subjects was classified from grade 0 to grade Ⅲ according to the method of an MRI grading system. FA, MD, AD, and RD maps were generated by postprocessing MUSE-DTI data on the GE workstation. Regions of interest (ROIs) were manually drawn at the C2 vertebral body level and C2/3-C6/7 intervertebral disc levels by covering the whole spinal cord. The clinical severity of myelopathy of subjects was assessed by the clinical Japanese Orthopedic Association scale (JOA). MUSE-DTI can acquire a high-resolution diffusion image compared to traditional DTI. The FA MCL values showed a decreasing trend from grade 0 to grade Ⅲ, while the MD MCL , AD MCL , and RD MCL values showed an overall increasing trend. Significant differences in MD MCL , AD MCL , and RD MCL values were found between adjacent groups among grades Ⅰ-Ⅲ (p<.05). The AD C2 values in CSM patients (grade I–Ⅲ) were significantly lower than in healthy individuals (grade 0) (p=.019). The clinical JOA score has a significant correlation with FA MCL (p=.035), MD MCL (p<.001), AD MCL (p<.001), and RD MCL (p<.001) values. MUSE-DTI displayed a better image quality compared to traditional DTI. MUSE-DTI parameters displayed a grade-dependent trend. All the MUSE-DTI parameters at MCL were correlated with the clinical JOA scores. The AD C2 values can reflect the secondary damage of distal spinal cord. Therefore, MUSE-DTI could be a reliable biomarker for clinical auxiliary diagnosis of spinal cord injury severity in cervical spondylotic myelopathy. [ABSTRACT FROM AUTHOR]

Anxiety is usually attributed to adverse environmental factors, but it is known as a polygenic inheritance disease. Gene-environment interactions on the occurrence and severity of anxiety are still unclear. The role of brain network connectivity in the gene-environment effects on anxiety has not been explored and may be key to understanding neuropathogenesis and guiding treatment. This study recruited 177 young adults from the community that completed functional magnetic resonance imaging, Childhood Trauma Questionnaire (CTQ), state-trait anxiety scores, and whole exome sequencing. We calculated polygenic risk score (PRS) for anxiety and the sum score of CTQ, which are genetic and environmental factors that may affect anxiety, respectively. Abnormal brain network connectivity determined by the gene-environment effects and its associations with anxiety scores were then explored. Except for the main effect of PRS or CTQ on intra-network connectivity, significant interactions were found in intra-network connectivity of visual network, default mode network, self-reference network, and sensorimotor network. Moreover, altered network connectivity was related to anxious tendency. In particular, the effect of CTQ on trait anxiety was mediated by the disrupted sensorimotor network, accompanied by a significant direct effect. However, the PRS influence on anxiety was mainly mediated through sensorimotor network paths, which exceeded the direct influence and was moderated by childhood trauma levels. These network-specific functional changes related to individual gene-environment risks advance our understanding of psychiatric pathogenesis of anxiety and provide new insights for clinical intervention. [Display omitted] • Altered brain networks determined by PRS and CTQ were related to anxiety. • Disrupted sensorimotor network mediated the effect of CTQ on anxiety. • The effects of PRS on anxiety through sensorimotor network were moderated by CTQ. [ABSTRACT FROM AUTHOR]

Xenogeneic extracellular matrix (ECM) based tissue engineering graft is one of the most promising products for transplantation therapies, which could alleviate the pain of patients and reduce surgery cost. However, in order to put ECM based xenografts into clinical use, the induced inflammatory and immune responses have yet to be resolved. Cell membrane is embedded with membrane proteins for regulation of cell interactions including self-recognition and potent in reducing foreign body rejections. In this study, a novel and facile method for evasion from immune system was developed by coating autologous red blood cell membrane as a disguise on xenogeneic ECM based tissue engineering graft surface. Porcine source Living Hyaline Cartilage Graft (LhCG) and decellularized LhCG (dLhCG) established by our group for cartilage tissue engineering were chosen as model grafts. The cell membrane coating was quite stable on xenografts with no obvious decrease in amount for 4 weeks. The autologous cell membrane coated xenograft has been proved to be recognized as "self" by immune system on cell, protein and gene levels according to the 14-day lasting in vivo study on rats with less inflammatory cells infiltrated and low inflammation-related cytokines gene expression, showing alleviated acute immune and inflammatory responses. [ABSTRACT FROM AUTHOR]

Articular cartilage repair has been a long-standing challenge in orthopaedic medicine due to the limited self-regenerative capability of cartilage tissue. Currently, cartilage lesions are often treated by microfracture or autologous chondrocyte implantation (ACI). However, these treatments are frequently reported to result in a mixture of the desired hyaline cartilage and mechanically inferior fibrocartilage. In this study, by combining the advantages of cartilage tissue engineering and decellularization technology, we developed a decellularized allogeneic hyaline cartilage graft, named dLhCG, which achieved superior efficacy in articular cartilage repair and surpassed living autologous chondrocyte-based cartilaginous engraftment and ACI. By the 6-month time point after implantation in porcine knee joints, the fine morphology, composition, phenotype, microstructure and mechanical properties of the regenerated hyaline-like cartilaginous neo-tissue have been demonstrated via histology, biochemical assays, DNA microarrays and mechanical tests. The articular cartilaginous engraftment with allogeneic dLhCG was indicated to be well consistent, compatible and integrated with the native cartilage of the host. The successful repair of articular chondral defects in large animal models suggests the readiness of allogeneic dLhCG for clinical trials. [ABSTRACT FROM AUTHOR]

Abstract Purpose: Texture analysis performed on MR images can detect quantitative features that are imperceptible to human visual assessment. The purpose of this study was to evaluate the feasibility of texture analysis on preoperative conventional MRI to discriminate between histological subtypes in low-grade gliomas (LGGs), and to determine the utility of texture analysis compared to histogram analysis alone. Methods: A total of 41 patients with LGG, 21 astrocytoma and 20 1p/19q codeleted oligodendroglioma were included in this study. Patients were randomly divided into training (60%) and testing (40%) sets. Texture analysis was performed on conventional MRI sequences to obtain the most discriminant factor (MDF) values for both the training and testing data. Receiver operating characteristic (ROC) curve analyses were then performed using the MDF values and 9 histogram parameters in the training data to obtain cut-off values for determining the correct rate of discriminating between astrocytoma and oligodendroglioma in the testing data. Results: The ROC analyses using MDF values resulted in an area under the curve (AUC) of 0.91 (sensitivity 86%, specificity 87%) for T2w FLAIR, 0.94 (87%, 89%) for ADC, 0.98 (93%, 95%) for T1w, and 0.88 (78%, 86%) for T1w + Gd sequences. Using the best cut-off values, MDF correctly discriminated between the two groups in 94%, 82%, 100%, and 88% of cases in the testing data, respectively. The MDF outperformed all 9 of the histogram parameters. Conclusion: Texture analysis performed on conventional preoperative MRI images can accurately predict histological subtype of LGGs, which would have an impact on clinical management. [ABSTRACT FROM AUTHOR]

Abstract Objectives To demonstrate the feasibility of the neurite orientation dispersion and density imaging (NODDI) technique in characterizing the microstructural changes in brain tissues during ischemic stroke and to compare its sensitivity with diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI). Methods Seventy-one patients with hyperacute/acute/subacute ischemic stroke were enrolled in the study. A multishell diffusion magnetic resonance imaging (dMRI) protocol was performed for each subject. Diffusion data were analyzed using the NODDI and diffusional kurtosis estimator toolboxes. Then, NODDI metrics between the lesions and the contralateral tissues were compared to evaluate their values in ischemic stroke. NODDI metrics among different stroke periods and the correlations between NODDI and the duration since stroke onset were analyzed as well. To compare the NODDI's sensitivity with established diffusion techniques, paired t -tests were performed to determine the absolute percentage changes of diffusion metrics between NODDI and DTI/DKI. Results Compared with the contralateral tissues, lesions showed significantly increased values of intracellular volume fraction (V ic) and orientation dispersion index (ODI) and decreased values of isotropic volume fraction (V iso). ODI value was significantly different among three periods and showed fair to good positive correlation with the duration since stroke onset (R = 0.450). NODDI metrics showed significantly larger absolute percentage changes than that of DTI and DKI (P < 0.05, respectively). Conclusion NODDI allowed efficient evaluation of microstructural changes in brain tissues during ischemic stroke and showed increased sensitivity compared with DTI and DKI. The possible biophysical mechanisms underlying ischemia could be further elucidated using this advanced diffusion technique. [ABSTRACT FROM AUTHOR]

Abstract Diffusion-weighted MRI (dMRI) is a key component of clinical radiology. When analyzing diffusion-weighted images, radiologists often seek to infer microscopic tissue structure through measurements of the diffusion coefficient, D 0 (mm2/s). This multi-scale problem is framed by the creation of diffusion models of signal decay based on physical laws, histological structure, and biophysical constraints. The purpose of this paper is to simplify the model building process by focusing on the observed decay in the effective diffusion coefficient as a function of diffusion weighting (b -value), D (b), that is often observed in complex biological tissues. We call this approach the varying diffusion curvature (VDC) model. Since this is a heuristic model, the exact functional form of this decay is not important, so here we examine a simple exponential function, D (b) = D 0 exp (−bD 1), where D 0 and D 1 capture aspects of hindered and restricted diffusion, respectively. As an example of the potential of the VDC model, we applied it to dMRI data collected from normal and diseased human brain tissue using Stejskal-Tanner diffusion gradient pulses. In order to illustrate the connection between D 0 and D 1 and the sub-voxel structure we also analyzed dMRI data from families of Sephadex beads selected with increasing tortuosity. Finally, we applied the VDC model to dMRI simulations of nested muscle fiber phantoms whose permeability, atrophy, and fiber size distribution could be changed. These results demonstrate that the VDC model is sensitive to sub-voxel tissue structure and composition (porosity, tortuosity, and permeability), hence can capture tissue complexity in a manner that could be easily applied in clinical dMRI. [ABSTRACT FROM AUTHOR]

Purpose: To compare the main parameters derived from monoexponential, biexponential and stretched-exponential diffusion-weighted imaging (DWI) and diffusion kurtosis imaging (DKI) with respect to diagnostic performance for tumor grading and proliferation assessment in diffuse astrocytic tumors (DATs).Materials and Methods: Fifty-eight pathologically confirmed DAT patients who underwent DWI and DKI on a 3-T scanner were prospectively collected and retrospectively reviewed. Measurements including the apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), distributed diffusion coefficient (DDC), heterogeneity index (α), mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK) were compared between tumor grades (Ⅱ, Ⅲ, and Ⅳ) by using a Jonckheere-Terpstra test. Receiver operating characteristic (ROC) curves were used to assess the diagnostic efficacy of these parameters. Spearman's rho with the Ki-67 labeling index (LI) was calculated for each parameter.Results: MK values differed significantly between all DAT subtypes and increased with grade. The ADC, D, f, DDC, α and MD values were significantly higher in grade Ⅱ tumors than in grade Ⅲ/Ⅳ tumors. D* values were significantly lower in grade Ⅱ tumors than in grade Ⅳ tumors (all P < 0.05). In discriminating between grade Ⅱ and Ⅲ tumors, α, MK, MD, D and f had significantly greater area under the ROC curve (AUC) values than D* and FA (0.927, 0.901, 0.896, 0.895, and 0.889, respectively vs 0.659 and 0.598, respectively, P < 0.05). In discriminating between grade Ⅲ and Ⅳ tumors, only MK demonstrated acceptable discrimination (AUC = 0.711). MK and D showed a strong correlation with the Ki-67 LI (ρ = 0.791 and -0.789, respectively, P < 0.001). D*, f, MD, ADC, DDC and α showed a moderate correlation (|ρ| ranged from 0.415 to 0.698, P < 0.05).Conclusion: MK and D have considerable potential to predict the degree of proliferation of DATs. MK could effectively characterize microstructural changes throughout the malignant transformation of DATs and provided useful complementary information for grading. [ABSTRACT FROM AUTHOR]

Background Anomalous diffusion model has been introduced and shown to be beneficial in clinical applications. However, only the directionally averaged values of anomalous diffusion parameters were investigated, and the anisotropy of anomalous diffusion remains unexplored. The aim of this study was to demonstrate the feasibility of using anisotropy of anomalous diffusion for differentiating low- and high-grade cerebral gliomas. Methods Diffusion MRI images were acquired from brain tumor patients and analyzed using the fractional motion (FM) model. Twenty-two patients with histopathologically confirmed gliomas were selected. An anisotropy metric for the FM-related parameters, including the Noah exponent ( α ) and the Hurst exponent ( H ), was introduced and their values were statistically compared between the low- and high-grade gliomas. Additionally, multivariate logistic regression analysis was performed to assess the combination of the anisotropy metric and the directionally averaged value for each parameter. The diagnostic performances for grading gliomas were evaluated using a receiver operating characteristic (ROC) analysis. Results The Hurst exponent H was more anisotropic in high-grade than in low-grade gliomas ( P  = 0.015), while no significant difference was observed for the anisotropy of α . The ROC analysis revealed that larger areas under the ROC curves were produced for the combination of α (1) and the combination of H (0.813) compared with the directionally averaged α (0.979) and H (0.594), indicating an improved performance for tumor differentiation. Conclusion The anisotropy of anomalous diffusion can provide distinctive information and benefit the differentiation of low- and high-grade gliomas. The utility of anisotropic anomalous diffusion may have an improved effect for investigating pathological changes in tissues. [ABSTRACT FROM AUTHOR]

• We extracted pre-adulthood urbanicity of 5,390 participants from remote sensing satellite data based on annual residential address of each participant. • Pre-adulthood urbanicity is positively correlated with volumes of bilateral fimbria and left subiculum body. • Pre-adulthood urbanicity has beneficial effects on neurocognitive abilities. • The volumes of left fimbria and left subiculum body mediated the relations between urbanicity and visuospatial memory. Urbanicity refers to the conditions that are particular to urban areas and is a growing environmental challenge that may affect hippocampus and neurocognition. This study aimed to investigate the effects of the average pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities as well as the sensitive age windows of the urbanicity effects. We included 5,390 CHIMGEN participants (3,538 females; age: 23.69 ± 2.26 years, range: 18–30 years). Pre-adulthood urbanicity of each participant was defined as the average value of annual night-time light (NL) or built-up% from age 0–18, which were extracted from remote-sensing satellite data based on annual residential coordinates of the participants. The hippocampal subfield volumes were calculated based on structural MRI and eight neurocognitive measures were assessed. The linear regression was applied to investigate the associations of pre-adulthood NL with hippocampal subfield volumes and neurocognitive abilities, mediation models were used to find the underlying pathways among urbanicity, hippocampus and neurocognition, and distributed lag models were used to identify sensitive age windows of urbanicity effect. Higher pre-adulthood NL was associated with greater volumes in the left (β = 0.100, 95%CI: [0.075, 0.125]) and right (0.078, [0.052, 0.103]) fimbria and left subiculum body (0.045, [0.020, 0.070]) and better neurocognitive abilities in information processing speed (-0.212, [-0.240, −0.183]), working memory (0.085, [0.057, 0.114]), episodic memory (0.107, [0.080, 0.135]), and immediate (0.094, [0.065, 0.123]) and delayed (0.087, [0.058, 0.116]) visuospatial recall, and hippocampal subfield volumes and visuospatial memory showed bilateral mediations for the urbanicity effects. Urbanicity effects were greatest on the fimbria in preschool and adolescence, on visuospatial memory and information processing from childhood to adolescence and on working memory after 14 years. These findings improve our understanding of the impact of urbanicity on hippocampus and neurocognitive abilities and will benefit for designing more targeted intervention for neurocognitive improvement. [ABSTRACT FROM AUTHOR]

We analyzed, in an integrative fashion, the morphometry and structural integrity of the bilateral hippocampi and amygdalas in Alzheimer's disease (AD) using T1-weighted images and diffusion tensor images (DTIs). We detected significant hippocampal and amygdalar volumetric atrophies in AD relative to healthy controls (HCs). Shape analysis revealed significant region-specific atrophies with the hippocampal atrophy mainly being concentrated on the CA1 and CA2 while the amygdalar atrophy was concentrated on the basolateral and basomedial. In all structures, the structural integrity displayed a significantly decreased mean fractional anisotropy (FA) value and an increased mean trace value in AD. In addition to the inter-group comparisons, we systematically evaluated the discriminative power of our three types of features (volume, shape, and DTI), both individually and in their possible combinations, when differentiating between AD and HCs. We found the volume features to be redundant when the more sophisticated shape features were available. A combination of the shape and DTI features of the right hippocampus, with classification automatically performed by support vector machine, yielded the strongest classification result (overall accuracy, 94.6%; sensitivity, 95.5%; specificity, 93.3%). [ABSTRACT FROM AUTHOR]

Purpose Diffusional kurtosis imaging (DKI), as a non-Gaussian diffusion model, has been applied in human and animal studies of ischemic stroke. This study aimed to intensively characterize the temporal evolution of DKI-derived variables in an experimental middle cerebral artery occlusion (MCAO) model, and to explore its potential application in ischemic stroke. Materials and methods Eleven MCAO rats and ten control rats underwent DKI and diffusion weighted imaging (DWI) scans, at different time points of 0.5, 2, 6, 12, 24 and 72 h after operation respectively. The infarct area in DKI- and DWI-derived variables was compared among different time points, and between different groups [INFARCTION, MIRROR, CONTROL-R (right side of the control group, the same side as in the infarction group), CONTROL-L (left side of the control group)] using repeated measures analysis of variance (ANOVA). The percent changes from normal to that in ischemic tissues and histology were also evaluated. Results In the infarct region, from 0.5 to 72 h, MK, K ∥ , K ⊥ demonstrated irregular high signal, whereas relative homogeneous low signals were revealed by MD, D ∥ , D ⊥ and ADC. Compared with the MIRROR and CONTROL-R group, MK, K ∥ , K ⊥ in the infarcted area increased aggressively which peaked at 12 h and gradually decreased; MD, D ∥ , D ⊥ and ADC decreased gradually until 12 h and then began to increase gradually; FA decreased rapidly from 0.5 to 72 h. MD, D ∥ and ADC were significantly different between Mirror and CONTROL-L group ( P < 0.05). Conclusion DKI can provide more detailed information to describe ischemic lesion, and has great potential application in ischemic stroke. [ABSTRACT FROM AUTHOR]

Objective To compare the results of magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS) patients. Methods Nineteen ALS patients and thirteen age-matched healthy controls underwent MRS and DTI between October 2013 and July 2014. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were collected as the quantitative results of the imaging study. The ALS functional rating scale-revised (ALSFRS-R) and disease progression rate were evaluated to assess patients' disability. The imaging study results were compared between ALS patients and healthy controls. The relationship between disability assessment and imaging study results was analyzed. Results NAA/Cr in the motor cortex and FA in the corticospinal tract (CST) of both sides were significantly lower in patients than controls. There was no significant difference between the two groups in Cho/Cr, tract length, tract volume, ADC or NAA. No relationship was found between ALSFRS-R and FA (r = 0.243, p = 0.316) in the right CST; NAA (r = 0.095, p = 0.699) or NAA/Cr (r = 0.172, p = 0.481) in the left motor cortex; or NAA (r = 0.320, p = 0.182) or NAA/Cr (r = 0.193, p = 0.492) in the right motor cortex. There was no relationship between the disease progression rate and FA, NAA, or NAA/Cr on either side. Conclusion NAA/Cr and FA can help diagnose ALS. Regional brain NAA/Cr and FA values could not assess the ALSFRS-R or disease progression rate. [ABSTRACT FROM AUTHOR]

Imaging markers derived from magnetic resonance images, together with machine learning techniques allow for the recognition of unique anatomical patterns and further differentiating Alzheimer's disease (AD) from normal states. T1-based imaging markers, especially volumetric patterns have demonstrated their discriminative potential, however, rely on the tissue abnormalities of gray matter alone. White matter abnormalities and their contribution to AD discrimination have been studied by measuring voxel-based intensities in diffusion tensor images (DTI); however, no systematic study has been done on the discriminative power of either region-of-interest (ROI)-based features from DTI or the combined features extracted from both T1 images and DTI. ROI-based analysis could potentially reduce the feature dimensionality of DTI indices, usually from more than 10e+5, to 10-150 which is almost equal to the order of magnitude with respect to volumetric features from T1. Therefore it allows for straight forward combination of intensity based landmarks of DTI indices and volumetric features of T1. In the present study, the feasibility of tract-based features related to Alzheimer's disease was first evaluated by measuring its discriminative capability using support vector machine on fractional anisotropy (FA) maps collected from 21 subjects with Alzheimer's disease and 15 normal controls. Then the performance of the tract-based FA+gray matter volumes-combined feature was evaluated by cross-validation. The combined feature yielded good classification result with 94.3% accuracy, 95.0% sensitivity, 93.3% specificity, and 0.96 area under the receiver operating characteristic curve. The tract-based FA and the tract-based FA+gray matter volumes-combined features are certified their feasibilities for the recognition of anatomical features and may serve to complement classification methods based on other imaging markers. [ABSTRACT FROM AUTHOR]

Glioma is the most common primary brain tumor and causes a disproportionate level of morbidity and mortality across a wide range of individuals. From previous clinical practices, definition of glioma margin is the key point for surgical resection. In order to outline the exact margin of glioma and provide a guide effect for the physicians both at pre-surgical planning stage and surgical resection stage, pH/temperature sensitive magnetic nanogels conjugated with Cy5.5-labled lactoferrin (Cy5.5-Lf-MPNA nanogels) were developed as a promising contrast agent. Due to its pH/te mperature sensitivity, Cy5.5-Lf-MPNA nanogels could change in its hydrophilic/hydrophobic properties and size at different pH and temperatures. Under physiological conditions (pH 7.4, 37 °C), Cy5.5-Lf-MPNA nanogels were hydrophilic and swollen, which could prolong the blood circulation time. In the acidic environment of tumor tissues (pH 6.8, 37 °C), Cy5.5-Lf-MPNA nanogels became hydrophobic and shrunken, which could be more easily accumulated in tumor tissue and internalized by tumor cells. In addition, lactoferrin, an effective targeting ligand for glioma, provides active tumor targeting ability. In vivo studies on rats bearing in situ glioma indicated that the MR/fluorescence imaging with high sensitivity and specificity could be acquired using Cy5.5-Lf-MPNA nanogels due to active targeting function of the Lf and enhancement of cellular uptake by tailoring the hydrophilic/hydrophobic properties of the nanogels. With good biocompatibility shown by cytotoxicity assay and histopathological analysis, Cy5.5-Lf-MPNA nanogels are hopeful to be developed as a specific and high-sensitive contrast agent for preoperative MRI and intraoperative fluorescence imaging of glioma. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine whether hippocampi alter in patients at the recovery stage of middle cerebral artery occlusion (MCAO) and whether the changes of hippocampi involve in the cognitive impairment in such patients. Meterials and methods: Forty-four patients with unilateral infarction solely in MCAO territory and 44 age-, sex- and education background-matched healthy volunteers were enrolled in this study. All subjects underwent 3-dimensional fast spoiled gradient-echo (3D FSPGR) and sing-voxel proton magnetic resonance spectroscopy (1H MRS) protocols at a 1.5T MR scanner. The ratios of n-acetylaspartate/creatine (NAA/Cr) and myo-inositol/creatine (mI/Cr) were obtained by using software integrated in the MR scanner. The hippocampal volumes were estimated by manually measurement. Results: The volume and NAA/Cr ratio were found significantly decreased and mI/Cr ratio significantly increased in the hippocampus ipsilateral to occluded middle cerebral artery (MCA) as compared with values in the contralateral hippocampus or healthy control. A reduced NAA/Cr ratio was also observed in contralateral hippocampus compared to controls. The shrinkage ratio of hippocampus ipsilateral to MCAO was found related to the Mini–Mental State Examination (MMSE) score. Conclusion: Our study identified that the hippocampal secondary damage occurred in patients after MCAO, and it could be evaluated noninvasively by volumetric magnetic resonance imaging (MRI) and 1H MRS. Moreover, the hippocampal secondary damage in MCAO patients indeed contributed to their cognitive impairment. [Copyright &y& Elsevier]

• MBDNF × CTQ interactions on morphological and functional connectivity of regions regulate emotion processing. • The Val/Val genotype with higher BDNF availability is more susceptible to experience-induced brain plasticity. • Childhood adversity contributes to functional plasticity of the self-reference network, increasing the risk of anxiety. Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may modulate the link between childhood trauma experience and psychopathology by altering trophic signaling on neuroplasticity. However, few multimodal magnetic resonance imaging (MRI) researches have investigated this gene-environment interaction on both structural and functional plasticity, thereby advancing knowledge about the etiology, prevention, and customized therapeutic directions of mental disease in individuals with childhood trauma experience. We recruited a large non-clinical sample of young adults that completed Childhood Trauma Questionnaire (CTQ), behavioral scores, multimodal MRI scans, and genotyping. Morphometric similarity network (MSN) and independent component analysis were adopted to quantify brain structural and functional changes. Gene-environment-brain-behavior relationships were identified by multiple regression and mediation effect analysis. CTQ score was positively associated with depression and anxiety scores. We found interactions on MSN in sensorimotor, temporal, and orbitofrontal cortex. For intra-network connectivity, significant interaction was noted in clusters within sensorimotor network. For inter-network connectivity, connectivity between dorsal attention network and salience network showed an interactive effect. For mean connectivity strength of each network, we found a main effect of CTQ score on self-reference network that was an outstanding mediator supporting the relationship between CTQ score and anxiety. Our findings demonstrate that childhood trauma and the BDNF Val66Met polymorphism are associated with brain plasticity involving emotion regulation, structurally and functionally, which may contribute to understanding psychotic mechanisms and predicting differential susceptibility. Imaging genetics may be useful as biomarkers to provide early assessment and guide cognitive interventions to avoid or decrease the risk of developing psychopathology. [ABSTRACT FROM AUTHOR]

• Proton exchange rate (k e x) imaging was proposed based on water direct saturation (DS)-removed omega plots. • k e x MRI can differentiate infarcts from contralateral normal brain tissues. • k e x MRI was different from conventional MRI contrasts. To map and quantify the proton exchange rate (k e x) of brain tissues using improved omega plots in ischemic stroke patients and to investigate whether k e x can serve as a potential endogenous surrogate imaging biomarker for detecting the metabolic state and the pathologic changes due to ischemic stroke. Three sets of Z-spectra were acquired from seventeen ischemic stroke patients using a spin echo-echo planar imaging sequence with pre-saturation chemical exchange saturation transfer (CEST) pulse at B 1 of 1.5, 2.5, and 3.5 μ T , respectively. Pixel-wise k e x was calculated from improved omega plot of water direct saturation (DS)-removed Z-spectral signals. The derived k e x maps can differentiate infarcts from contralateral normal brain tissues with significantly increased signal (893 ± 52 s - 1 vs. 739 ± 34 s - 1 , P < 0.001). The k e x maps were found to be different from conventional contrasts from diffusion-weighted imaging (DWI), CEST, and semi-solid magnetization transfer (MT) MRI. In brief, k e x MRI showed larger lesion areas than DWI with different degrees and different lesion contrast compared to CEST and MT. In this preliminary translational research, the k e x MRI based on DS-removed omega plots has been demonstrated for in vivo imaging of clinical ischemic stroke patients. As a noninvasive and unique MRI contrast, k e x MRI at 3 T may serve as a potential surrogate imaging biomarker for the metabolic changes of stroke and help for monitoring the evolution and the treatment of stroke. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate hemodynamic changes (volume, velocity, wall shear stress, pressure gradient, and energy loss) in the common carotid artery (CCA) and internal carotid artery (ICA) of healthy adults among different ages and anatomical locations using 4D flow MRI.Methods: Sixty-two healthy volunteers aged 20-75 years were enrolled in this study. 4D flow MRI examinations were performed for each subject and were analyzed using the CVI42 platform to generate hemodynamic parameters. Hemodynamic parameters were compared among different age groups and anatomical locations (proximal CCA, distal CCA, proximal ICA and distal CCA) using one-way ANOVA. The paired t-test was used to estimate the differences between left and right vessels. The relationship between age and hemodynamic parameters was quantified by Pearson's correlation coefficient.Results: There were no differences between the left and right carotid arteries for any of the hemodynamic parameters (all p values > 0.05), so we set each vessel as an independent sample. The proximal ICA had significantly lower volume, velocity, wall shear stress, and pressure gradient values than the values determined for other locations (p < 0.05), and energy loss was similar among different locations. Wall shear stress (except in the distal ICA), velocity, pressure gradient, and energy loss decreased with age (p < 0.05).Conclusions: The multiparameter analysis of 4D flow MRI can identify age and anatomical location changes in hemodynamic parameters in the carotid arteries of healthy adults. The lower velocity, wall shear stress, and pressure gradient in the proximal ICA and the reduced trend with age may be associated with disease occurrence. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the alterations of brain volumetry and associated structural covariance at lobar level in cerebral small-vessel disease (CSVD) with and without cognitive impairment.Method: Twenty-seven CSVD patients with mild cognitive impairment (CSVD-MCI), 37 CSVD patients with normal cognition (CSVD-NC), and 35 controls, underwent T1-weighted imaging of magnetic resonance. Volume of gray matter (GM) and white matter (WM) and a lobar atrophy index that measures the ratio of cerebrospinal fluid to brain parenchyma were quantified for each lobe. One-way ANOVA with multiple comparison corrections was performed to compare these volumetric measures. Volumetric structural covariance analyses were performed with lobar atrophy indexes to investigate the alterations of anatomical covariance within each pair of lobar regions in CSVD-NC and CSVD-MCI subjects compared with controls.Results: CSVD-NC subjects presented no significant volumetric differences with controls in any of the lobar regions. Compared with controls, CSVD-MCI patients presented significantly smaller volume of GM in bilateral frontal and parietal lobes, significantly smaller volume of WM in right cingulate lobe, and significantly larger lobar atrophy indexes of bilateral temporal, insular lobes and left cingulate lobe (P < 0.05). Both CSVD-NC group and CSVD-MCI group showed significant differences of structural covariance as measured by lobar atrophy index compared with controls. In particular, CSVD-MCI group showed even more extensive alterations of structural covariance, especially in bilateral cingulate and temporal lobes.Conclusions: There are alterations of brain volumetry and associated structural covariance within lobar regions in CSVD, which indicates the potential brain structural reorganization in CSVD. [ABSTRACT FROM AUTHOR]

Purpose: To characterize brown adipose tissue (BAT) in polycystic ovary syndrome (PCOS) patients in comparison to healthy subjects using Z-spectral imaging (ZSI).Method: ZSI data were collected on 19 normal control females (NCF), 17 males (NCM), and 13 PCOS patients. By fitting to multiple Lorentzian functions, ZSI provides fat-water fraction (FWF) of tissue in the supraclavicular area that can be used to differentiate between white adipose tissue (WAT), BAT, and muscle. The fraction of BAT over the total fat depot (BATf) and the average FWF in BAT or FWF(BAT) were then computed, reflecting relative BAT mass and BAT metabolism respectively. The parameters were compared among the three groups, and the correlations to Body Mass Index (BMI) were also quantified.Results: There was an inverse correlation between BATf and BMI in normal subjects. The BATf of the PCOS group was significantly smaller than the NCF (P < 0.001). On the other hand, FWF(BAT) correlated linearly with BMI in healthy subjects. The PCOS group had higher FWF(BAT) than the NCF group (P < 0.001).Conclusions: Normal subjects with higher BMI show less BATf and have increased FWF(BAT), indicating relatively higher level of metabolic passive WAT depot and relatively reduced metabolism in their BAT depots. PCOS patients have the least BATf and the highest FWF(BAT), suggesting decreased BAT mass and function in PCOS. Novel imaging technique with ZSI for the characterization of BAT mass and function in PCOS may help to monitor treatment responses of PCOS therapies. [ABSTRACT FROM AUTHOR]

Purpose: To characterise the pattern of change of diffusional kurtosis imaging (DKI) parameters (including kurtosis and diffusion parameters) in both white matter and gray matter in normal brain development with a large sample of subjects from term-born neonates to 14-years old children.Methods: Two hundred and eighteen normal children (136 male, 82 female) underwent conventional magnetic resonance imaging and DKI. Regions of interest (ROIs) were placed in 7 white matter areas and 4 gray matter areas. Then the DKI-derived parameters were automatically calculated, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), radial diffusivity (Dr), mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Kr). The correlation between the DKI parameters and ages were analyzed using nonlinear fit, and the rate of parameter change was computed compared to the baseline value of the neonates.Results: For all ROIs in the white matter and gray matter, the FA, MK, Kr, Ka values increased with age, while the MD and Dr values decreased with age. The correlations were good to excellent, which changed rapidly within the first 2 years and relatively slowly after 2 years. The Da values in peripheral white matters and some gray matter structures (caudate nucleus and putamen) decreased with age. The amplitude of kurtosis parameters variation was greater than that of the diffusion parameters in both white matter and gray matter.Conclusions: The DKI parameters correlated well with age, and kurtosis parameters showed a potential advantage in detecting the normal brain development of children. [ABSTRACT FROM AUTHOR]

Purpose: On MR imaging, peritumoral T2 hyperintensity surrounding glioblastoma is known to contain tumor cell infiltrates, thus contributing to poor prognosis. This study aimed to determine the incremental prognostic value of radiomics on peritumoral T2 hyperintensity in pretreatment glioblastoma.Methods: One hundred fourteen pathologically confirmed glioblastoma patients were retrospectively selected from March 2008 to May 2018 (our institution, n = 61; the Cancer Imaging Archive, n = 53). All patients were randomly divided into either training (n = 80) or test set (n = 34). Manually segmented peritumoral T2 hyperintensity yielded 106 radiomic features per patient. A random forest variable selection was used to select the most relevant radiomic features. Four Cox proportional hazards models were fitted with clinical features, clinical features with tumor/peritumoral volumes, radiomics, and all of them combined. Kaplan-Meier survival curves of the models were plotted with log-rank tests. All models were validated on a test set using prediction error curves over survival times.Results: A random forest variable selection yielded five relevant features among the 106 radiomic features (two shape, two gray-level and one first order features). These radiomic features increased survival prediction accuracy when they were added onto clinical and tumor/peritumoral volumetric features (combined model, P = 0.011). On test set, the combined model showed lower mean survival prediction error rate (0.14) than clinical (0.191) or radiomic (0.178) model.Conclusions: The clinical model with radiomic features demonstrated improved survival predictive performance than the model without radiomic features, thus suggesting incremental prognostic value of peritumoral radiomics as MR imaging biomarker in pretreatment glioblastoma. [ABSTRACT FROM AUTHOR]