Imaging Session Research Articles

Assessment of macular findings by OCT angiography in patients without clinical signs of diabetic retinopathy: radiomics features for early screening of diabetic retinopathy

This cross-sectional study aimed to quantitatively analyze the optical coherence tomography angiography (OCTA) images using MATLAB-based software and evaluate the initial changes in macular vascular density and the distortion of the foveal avascular zone (FAZ), before the clinical appearance of diabetic retinopathy. For this purpose, 21 diabetic patients without any clinical features indicating DR, and 21 healthy individuals matched with patients based on their demographic characteristics were included. Macular thickness, macular vascular density, and morphological changes of FAZ were assessed using OCTA. The diagnostic ability of morphological parameters was evaluated by receiver operating curve analysis. The intraclass correlation coefficient (ICCC) index was used to check the consistency of the extracted values. There was no significant difference in age, gender, LogMAR visual acuity, spherical equivalent, and intra-ocular pressure amongst patients and controls. No correlation was found between age and the FAZ area as well as vascular density. The vascular structure of the superficial layer showed FAZ enlargement, reduced vascular density in the macular area, and significant deviations of FAZ shape parameters (convexity and Frequency Domain Irregularity) in patients compared with healthy individuals. Measurements were highly correlated between separate imaging sessions with ICCC of over 0.85 for all parameters. The represented data suggests that radiomics parameters can be applied as both an early screening tool and guidance for better follow-up of diabetic patients who have not had any sign of DR in fundoscopic exams.

Long Term Time-Lapse Imaging of Geographic Atrophy: A Pilot Study.

Geographic atrophy (GA), the late stage of age-related macular degeneration, is a major cause of visual disability whose pathophysiology remains largely unknown. Modern fundus imaging and histology revealed the complexity of the cellular changes that accompanies atrophy. Documenting the activity of the disease in the margins of atrophy, where the transition from health to disease occurs, would contribute to a better understanding of the progression of GA. Time-lapse imaging facilitates the identification of structural continuities in changing environments. In this retrospective pilot study, we documented the long-term changes in atrophy margins by time-lapse imaging of infrared scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) images in 6 cases of GA covering a mean period of 32.8 months (range, 18–72). The mean interval between imaging sessions was 2.4 months (range, 1.4–3.8). By viewing time-lapse sequences we observed extensive changes in the pattern of marginal hyperreflective spots, which associated fragmentation, increase and/or disappearance. Over the entire span of the follow-up, the most striking changes were those affecting hyperreflective spots closest to margins of atrophy, on the non-atrophic side of the retina; a continuum between the successive positions of some of the hyperreflective spots was detected, both by SLO and OCT. This continuum in their successive positions resulted in a subjective impression of a centrifugal motion of hyperreflective spots ahead of atrophy progression. Such mobilization of hyperreflective spots was detected up to several hundred microns away from atrophic borders. Such process is likely to reflect the inflammatory and degenerative process underlying GA progression and hence deserves further investigations. These results highlight the interest of multimodal time-lapse imaging to document cell-scale dynamics during progression of GA.Clinical Trial Registrationclinicaltrials.gov, identifier: NCT04128150 and NCT04129021.

Artificially-reconstructed brain images with stroke lesions from non-imaging data: modeling in categorized patients based on lesion occurrence and sparsity

Brain imaging is necessary for understanding disease symptoms, including stroke. However, frequent imaging procedures encounter practical limitations. Estimating the brain information (e.g., lesions) without imaging sessions is beneficial for this scenario. Prospective estimating variables are non-imaging data collected from standard tests. Therefore, the current study aims to examine the variable feasibility for modelling lesion locations. Heterogeneous variables were employed in the multivariate logistic regression. Furthermore, patients were categorized (i.e., unsupervised clustering through k-means method) by the charasteristics of lesion occurrence (i.e., ratio between the lesioned and total regions) and sparsity (i.e., density measure of lesion occurrences across regions). Considering those charasteristics in models improved estimation performances. Lesions (116 regions in Automated Anatomical Labeling) were adequately predicted (sensitivity: 80.0–87.5% in median). We confirmed that the usability of models was extendable to different resolution levels in the brain region of interest (e.g., lobes, hemispheres). Patients’ charateristics (i.e., occurrence and sparsity) might also be explained by the non-imaging data as well. Advantages of the current approach can be experienced by any patients (i.e., with or without imaging sessions) in any clinical facilities (i.e., with or without imaging instrumentation).

Abstract 1662: Orthotopic model of hepatocellular carcinoma (HCC) using Huh-7 and HepG2: Application of micro-CT in detection of cancer progression

Abstract Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and was listed as the third cause of death by cancer in 2020 (WHO). Hepatocarcinogenesis is a multistep process and to date it is still poorly understood. HCC occurs almost entirely in patients with underlying chronic liver disease and cirrhosis. Pre-clinical animal models play an important role in unveiling cancer biology which can facilitate development and testing of new antineoplastic drugs. The aim of this study was to establish an orthotopic model of HCC utilizing two cell lines Huh-7 and HepG2, which could be effectively used to study efficacy of new potential treatments. In a follow up study, the correlation of tumor marker alpha-fetoprotein (AFP) and tumor growth was investigated. AFP was measured using Quantikine® ELISA kit. For the intrahepatic (ih) inoculation cancer cells were injected into the left lobe of the liver. For the intrasplenic (is) inoculations of HCC cells, the spleen was exposed, and cells were injected into spleen parenchyma along the long axis of the spleen. Afterwards spleen was removed to avoid intrasplenic tumor growth. The animals were weighed two times a week throughout the study and appearance of any clinical signs was closely monitored. The animals were terminated 70 days after cancer cell implantation. The mice did not present with any acute symptoms before the end stage disease. However, prior sacrifice some swelling and darkening of the abdominal area especially in the ih-model was observed. To visualize liver ExiTron Nano 6000 nanoparticle contrast agent was used. The contrast agent was administered intravenously once during the study, prior the first imaging. Disease progression was monitored using Bruker SkyScan 1276 High-Resolution Micro-CT Scanner. The in vivo measurements were performed using one field of view (FOV) and an image pixel size of 18 μm. Each in vivo scanning was completed within 12 minutes and the estimated radiation dose was kept under 500 mGy at each imaging session. The first tumours were detected by µCT between 2-3 weeks depending more on the cancer cell implantation route than the cell line used. The take rate in the liver was 85% in the ih-model, and less than 50% in the is-model. The intrahepatic inoculation led to more uniform and measurable tumor nodules observed in majority of operated animals, whereas the intrasplenic tumors were dispersed throughout with multiple nodules. In addition, a tight correlation between tumor volume and amount of alpha-fetoprotein detected from serum samples was found. In conclusion, an orthotopic model using intrahepatic approach of cancer cells implantation was established. Application of µCT enabled following tumor growth and recognition of cancer spread in the abdomen. Altogether this provides a promising tool contributing to the development of novel therapies targeting HCC in vivo. Citation Format: Justyna Zdrojewska, Mari Suominen, Shirin Katoozi, Katja Fagerlund, Jukka Rissanen, Roger Malerbakken-Bjerke, Jenny Karlsson. Orthotopic model of hepatocellular carcinoma (HCC) using Huh-7 and HepG2: Application of micro-CT in detection of cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1662.

Abstract 2736: Forecasting treatment response to neoadjuvant therapy in triple-negative breast cancer via an image-guided digital twin

Abstract Introduction: Patients with locally advanced, triple-negative breast cancer (TNBC) typically receive neoadjuvant therapy (NAT) to downstage the tumor and to improve the outcome of subsequent breast conservation surgery. There are currently no methods to accurately predict how a TNBC patient will respond to NAT before surgery. In this work, we applied a digital twin framework to address this unmet clinical need, by integrating quantitative magnetic resonance imaging (MRI) data with mechanism-based mathematical modeling. Methods: Multiparametric MRI was acquired in patients (N = 50) before, after 2 and 4 cycles of Adriamycin/Cyclophosphamide (A/C), and again after 12 cycles of Paclitaxel as part of the ARTEMIS (NCT02276433) trial. Within each imaging session, dynamic contrast-enhanced (DCE) MRI, diffusion-weighted imaging (DWI), and a pre-contrast T1-map were acquired. The images were processed by a pipeline consisting of motion correction, multiparametric image alignment, inter-visit image registration to align the tumor and surrounding breast tissue, tissue segmentation, and estimation of tumor cellularity from DWI. A mechanism-based mathematical model, a reaction-diffusion equation, is used to characterize the mobility of tumor cells via diffusion damped by mechanical tissue properties, tumor proliferation via logistic growth, and treatment-induced cell death via the delivery and decay of therapies. For each patient, pre-treatment images were used for model initialization. The model calibration and prediction were implemented with two strategies: 1) using images acquired during the A/C for calibration and predicting up to the end of A/C, and 2) using images acquired during and after the A/C for calibration and predicting up to the end of NAT. For strategy 1), we evaluated the model by comparing its predicted tumor volume and total tumor cellularity to the imaging measurements at the end of A/C. For strategy 2), we evaluated the model by comparing its predicted final response to the post-surgical pathological findings. Results: For strategy 1), our framework predicted the change of tumor volume and total tumor cellularity with Pearson correlation coefficients of 0.91 and 0.89, respectively. Regarding strategy 2), our framework achieved an area under the receiver operator characteristic curve of 0.88 for distinguishing pCR from non-pCR. As a comparison, imaging measurement of tumor volume at the end of A/C achieved an AUC of 0.79. Conclusion: Our approach successfully captures the patient-specific dynamics of TNBC response to NAT and provides an improved prediction of final response, which demonstrates the potential of a digital twin framework to be a powerful tool for predicting response to NAT. Once validated, the method will provide a unique opportunity for optimizing treatment plans on a patient-specific basis. Citation Format: Chengyue Wu, Angela M. Jarrett, Zijian Zhou, Nabil Elshafeey, Beatriz E. Adrada, Rosalind P. Candelaria, Rania Mohamed, Medine Boge, Lei Huo, Jason White, Debu Tripathy, Vicente Valero, Jennifer Litton, Clinton Yam, Jong Bum Son, Jingfei Ma, Gaiane M. Rauch, Thomas E. Yankeelov. Forecasting treatment response to neoadjuvant therapy in triple-negative breast cancer via an image-guided digital twin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2736.

Uncovering individual differences in fine-scale dynamics of functional connectivity.

Functional connectivity (FC) profiles contain subject-specific features that are conserved across time and have potential to capture brain-behavior relationships. Most prior work has focused on spatial features (nodes and systems) of these FC fingerprints, computed over entire imaging sessions. We propose a method for temporally filtering FC, which allows selecting specific moments in time while also maintaining the spatial pattern of node-based activity. To this end, we leverage a recently proposed decomposition of FC into edge time series (eTS). We systematically analyze functional magnetic resonance imaging frames to define features that enhance identifiability across multiple fingerprinting metrics, similarity metrics, and data sets. Results show that these metrics characteristically vary with eTS cofluctuation amplitude, similarity of frames within a run, transition velocity, and expression of functional systems. We further show that data-driven optimization of features that maximize fingerprinting metrics isolates multiple spatial patterns of system expression at specific moments in time. Selecting just 10% of the data can yield stronger fingerprints than are obtained from the full data set. Our findings support the idea that FC fingerprints are differentially expressed across time and suggest that multiple distinct fingerprints can be identified when spatial and temporal characteristics are considered simultaneously.

Repeatability of radiotherapy dose-painting prescriptions derived from a multiparametric magnetic resonance imaging model of glioblastoma infiltration.

Glioblastoma (GBM) patients have a dismal prognosis. Tumours typically recur within months of surgical resection and post-operative chemoradiation. Multiparametric magnetic resonance imaging (mpMRI) biomarkers promise to improve GBM outcomes by identifying likely regions of infiltrative tumour in tumour probability (TP) maps. These regions could be treated with escalated dose via dose-painting radiotherapy to achieve higher rates of tumour control. Crucial to the technical validation of dose-painting using imaging biomarkers is the repeatability of the derived dose prescriptions. Here, we quantify repeatability of dose-painting prescriptions derived from mpMRI. TP maps were calculated with a clinically validated model that linearly combined apparent diffusion coefficient (ADC) and relative cerebral blood volume (rBV) or ADC and relative cerebral blood flow (rBF) data. Maps were developed for 11 GBM patients who received two mpMRI scans separated by a short interval prior to chemoradiation treatment. A linear dose mapping function was applied to obtain dose-painting prescription (DP) maps for each session. Voxel-wise and group-wise repeatability metrics were calculated for parametric, TP and DP maps within radiotherapy margins. DP maps derived from mpMRI were repeatable between imaging sessions (ICC>0.85). ADC maps showed higher repeatability than rBV and rBF maps (Wilcoxon test, p=0.001). TP maps obtained from the combination of ADC and rBF were the most stable (median ICC: 0.89). Dose-painting prescriptions derived from a mpMRI model of tumour infiltration have a good level of repeatability and can be used to generate reliable dose-painting plans for GBM patients.

Novel imaging techniques for sacroiliac joint assessment.

Imaging of the sacroiliac joints is one of the cornerstones in the diagnosis and monitoring of axial spondyloarthritis. We aim to present an overview of the emerging imaging techniques for sacroiliac joint assessment and provide an insight into their relevant benefits and pitfalls. Evaluation of structural and active inflammatory lesions in sacroiliitis are both important for understanding the disease process. Dual-energy computed tomography (CT) can detect inflammatory bone marrow edema in the sacroiliac joints and provides an alternative for magnetic resonance imaging (MRI). Three-dimensional gradient echo sequences improve the visualization of erosions on MRI. Susceptibility weighted MRI and deep learning-based synthetic CT are innovative MRI techniques that allow for generating 'CT-like' images and better depict osseous structural lesions than routine MRI sequences. New imaging innovations and developments result in significant improvements in the imaging of spondyloarthritis. Advanced MRI techniques enhance its potential for the accurate detection of structural and active inflammatory lesions of sacroiliitis in one single imaging session.

Gray's Impulsivity Is Differentially Associated With Amygdala-Insula Functional Connectivity in Adolescents, Depending on ADHD Risk Status

AimsAttention-Deficit/Hyperactivity Disorder (ADHD) is associated with alterations in both reinforcement sensitivity and affective processing but the nature of the associations of these characteristics is yet to be examined. We hypothesized that individual differences in the sensitivity of the Behavioral Approach System (BAS) would exhibit differential relations with affective network connectivity – involved in emotional regulation and salience monitoring – in youth at-risk for, relative to youth not at-risk for, ADHD.MethodsAdolescents (n = 125; Mage=16.24 years, SD = 1.09 years; 61.6% boys) were recruited as part of The Budapest Longitudinal Study of ADHD and Externalizing Disorders. Forty-nine were classified as at-risk for ADHD (Mage=16.15 years; SD = 1.21 years; 77.6% boys), defined as exhibiting ≥4 parent-rated symptoms of either domain on the ADHD Rating Scale-5. Participants completed a 10-minute resting-state functional Magnetic Resonance Imaging session, during which they were asked to focus their attention on a fixation cross, as well as various self-report assessments, including the Reinforcement Sensitivity Theory of Personality Questionnaire (RST-PQ).ResultsFunctional Network Connectivity analyses indicated an interaction effect between the RST-PQ BAS impulsivity subscale and at-risk status on functional connectivity between four affective network region-pairs (ps < .05, False Discovery Rate [FDR] corrected) within a cluster based on functional similarity (p = .014, FDR-corrected). Follow-up OLS linear regressions showed higher impulsivity scores predicted stronger functional connectivity between the (1) left amygdala-right insula (F(6, 117) = 3.298, p = .005, adjusted R2=.101), (2) left amygdala-left insula (F(6, 117) = 2.2, p = .048, adjusted R2=.055), (3) right amygdala-right insula (F(6, 117) = 3.833, p = .002, adjusted R2=.121), and (4) right amygdala-left insula (F(6, 117) = 3.064, p = .008, adjusted R2=.092) in at-risk youth, whereas an inverse relationship was apparent in not at-risk youth.There was no main effect of group status on BAS impulsivity scores (t(122)=−1.167, p = .246) or on functional connectivity ((1) t(122) = .383, p = .702; (2) t(122) = .195, p = .846; (3) t(122)=−.107, p = .915; (4) t(122)=−.206, p = .837).ConclusionThe amygdala-insula connection has been shown to be involved in trait impulsivity, however, available ADHD-focused studies targeted emotional functioning. To our knowledge, we are the first to demonstrate that Gray's impulsivity – reflecting trait reward sensitivity – is predictive of amygdala-insula functional connectivity at rest and that this relation differs given ADHD risk. Results have conceptual and practical implications (e.g., early identification) as the role of the amygdala-insula connection in reward sensitivity appears especially relevant for a developmental phase and a diagnostic group linked to increased risk taking.

Vagus Nerve Sensory Neurons Respond Distinctly to Specific Inflammatory Mediators

The peripheral nervous system communicates with the immune system in response to injury or infection. In the case of inflammation, sensory signals travel up to the brain via the vagus nerve, which is a major pathway for neuro‐immune communication. While previous work from our group showed that cytokines administered systemically were associated with specific patterns of vagus nerve activity, we did not know how individual vagal sensory neurons encoded this immune information.Here, we use in vivo calcium imaging to monitor the neural activity of individual vagal sensory neurons in response to specific inflammatory mediators. Using mice that express the calcium sensor GCaMP6f in glutamatergic neurons, we imaged neurons of the nodose ganglion in situ using a 1‐photon miniature microscope (Miniscope). During imaging, the inflammatory mediators tumor necrosis factor (TNF) and interleukin 1β (IL‐1β) were applied directly to the vagus nerve. The raw fluorescence data was analyzed with a Python‐based calcium imaging analysis (CaImAn) software and a customized pipelines to output the neural activity (change in fluorescence: ∆F) of individually detected neurons. An average of 69±16.3 neurons were recorded per 1 hour imaging session.Our results reveal that specific vagal sensory neurons respond to differentially to specific immune mediators. The average amplitude, integral, and delay of TNF‐responsive neurons was significantly higher than IL‐1β‐responsive cells (TNF vs IL‐1β, p < 0.01). This result suggests that TNF application triggers responses later and with higher firing rates in responsive neurons compared to IL‐1β. Neuronal responses to IL‐1β had a significantly higher number of peaks when compared to TNF responses (IL‐1β vs TNF, p < 0.05). When compared to responses for the TRPV1‐specific agonist capsaicin, the cytokine responses were found to have significantly lower number of peaks (capsaicin vs IL‐1β, p < 0.05), which suggests that immune mediators produce different neural activity than canonical activators. Taken together, our findings demonstrate that individual vagal sensory neurons encode information about distinct inflammatory stimuli and provide insight into the neural sensing of inflammation. Further investigation into this type of neuro‐immune signaling may identify novel neural targets for the treatment of inflammatory disorders.

Summing up 10 years in a new medical school: Per aspera ad astra

Opening a new medical school and introducing an anatomy course is a rare opportunity for medical anatomy educators. Here we sum our experience in an ongoing 10‐year anatomy program, emphasizing the challenges we endured, the hardships and successes in the hope that others can learn from our experience.In February 2010, Bar Ilan University was chosen by the Israeli Council for Higher Education to open a new, fifth, medical faculty. A mere eight months later, the school opened its gates to a class of 70 students in the northern city of Safed. This new faculty, dedicated to establishing connections to the local community, enabled us to develop and implement a new anatomy curriculum.The basic course incorporated frontal lectures, dissection labs, basic systematic physiology, clinical correlation lectures and imaging labs. The initial curriculum included trunk and Head & neck regions spanning 5 weeks. After the first couple of years, the length and contents of the course started to change and adapt according to the needs of our faculty, and by input from physicians as well as students. Over the years student number rose to 100, and the course expanded to 10 weeks to incorporate the entire body aside from neuroanatomy, which is taught in a separate course. Histology and embryology were included; ultrasound hands‐on labs were added; and virtual anatomy sessions were integrated to the program. Clinical and physiological correlate lectures were cut down, with the understating, backed by students’ evaluations, that this was too early for them, and focus should remain on basic normal anatomy. On the other hand, more time was added to imaging sessions and lectures, as most modern physicians use these techniques in their everyday clinical practice. While originally relaying on retired physicians to serve as dissection instructors, we initialed a near‐peer students dissection instructors’ program that was met with great success.In the last couple of years our program and indeed the entire medical school was heavily impacted by the ongoing Covid‐19 pandemic. While lectures were taken to virtual platform, we decided to continue dissection sessions as normally as possible, with strict mandatory regulations including personal protective gear and keeping students’ number within the lab to a minimum of 15, 7‐8 students per cadaver. Students were highly appreciative of our efforts, and course scoring was exceptionally high.The last 10 years has shown us that anatomy, a basic and important tradition, could be taught in many exceptional ways, and we should always strive to improve. But perhaps even more important is the understating that we are educators to whom our students look up to, and endurance, perseverance, resourcefulness, and professionalism are just as important as scholastic knowledge.

PatchWarp: Corrections of non-uniform image distortions in two-photon calcium imaging data by patchwork affine transformations

SummaryComplex distortions on calcium imaging often impair image registration accuracy. Here, we developed a registration algorithm, PatchWarp, to robustly correct slow image distortion for calcium imaging data. PatchWarp is a two-step algorithm with rigid and non-rigid image registrations. To correct non-uniform image distortions, it splits the imaging field and estimates the best affine transformation matrix for each of the subfields. The distortion-corrected subfields are stitched together like a patchwork to reconstruct the distortion-corrected imaging field. We show that PatchWarp robustly corrects image distortions of calcium imaging data collected from various cortical areas through glass window or gradient-index (GRIN) lens with a higher accuracy than existing non-rigid algorithms. Furthermore, it provides a fully automated method of registering images from different imaging sessions for longitudinal neural activity analyses. PatchWarp improves the quality of neural activity analyses and is useful as a general approach to correct image distortions in a wide range of disciplines.

Fatty acid amide hydrolase levels in brain linked with threat-related amygdala activation

BackgroundPreclinical evidence suggests that increasing levels of the major endocannabinoid anandamide decreases anxiety and fear responses potentially through its effects in the amygdala. Here we used neuroimaging to test the hypothesis that lower fatty acid amide hydrolase (FAAH), the main catabolic enzyme for anandamide, is associated with a blunted amygdala response to threat. MethodsTwenty-eight healthy participants completed a positron emission tomography (PET) scan with the radiotracer for FAAH, [11C]CURB, as well as a block-design functional magnetic resonance imaging session during which angry and fearful faces meant to activate the amygdala were presented. Results[11C]CURB binding in the amygdala as well as in the medial prefrontal cortex, cingulate and hippocampus correlated positively with blood-oxygen-level-dependent (BOLD) signal during processing of angry and fearful faces (pFWE < 0.05). ConclusionOur finding that lower levels of FAAH in amygdala, medial prefrontal cortex, cingulate and hippocampus was associated with a dampened amygdala response to a threatening social cue aligns with preclinical and neuroimaging studies in humans and suggests the involvement of FAAH in modulating stress and anxiety in humans. The current neuroimaging study also lends support for the potential use of FAAH inhibitors to control amygdala hyperactivity, which is known to be involved in the pathophysiology of anxiety and trauma-related disorders.

Neural cognitive control moderates the longitudinal link between hedonia and substance use across adolescence

Hedonic dysregulation is evident in addiction and substance use disorders, but it is not clearly understood how hedonic processes may interact with brain development related to cognitive control to influence risky decision making and substance use during adolescence. The present study used prospective longitudinal data to clarify the role of cognitive control in the link between hedonic experiences and the development of substance use during adolescence. Participants included 167 adolescents (53% male) assessed at four time points, annually. Adolescents participated in a functional magnetic resonance imaging (fMRI) session where blood-oxygen level dependent (BOLD) response was monitored during the Multi-Source- Interference Task to assess cognitive control. Substance use and hedonia were assessed using self-report. A two-group growth curve model of substance use with hedonia as a time-varying covariate indicated that higher levels of hedonia predicted higher substance use, but only in adolescents with higher activation in the frontoparietal regions and in the rostral anterior cingulate cortex during cognitive control. Results elucidate the moderating effects of neural cognitive control on associations between hedonia and adolescent substance use, suggesting that lower cognitive control functioning in the brain may exacerbate risk for substance use promoted by hedonia.

MRA-free intracranial vessel localization on MR vessel wall images

Analysis of vessel morphology is important in assessing intracranial atherosclerosis disease (ICAD). Recently, magnetic resonance (MR) vessel wall imaging (VWI) has been introduced to image ICAD and characterize morphology for atherosclerotic lesions. In order to automatically perform quantitative analysis on VWI data, MR angiography (MRA) acquired in the same imaging session is typically used to localize the vessel segments of interest. However, MRA may be unavailable caused by the lack or failure of the sequence in a VWI protocol. This study aims to investigate the feasibility to infer the vessel location directly from VWI. We propose to synergize an atlas-based method to preserve general vessel structure topology with a deep learning network in the motion field domain to correct the residual geometric error. Performance is quantified by examining the agreement between the extracted vessel structures from the pair-acquired and alignment-corrected angiogram, and the estimated output using a cross-validation scheme. Our proposed pipeline yields clinically feasible performance in localizing intracranial vessels, demonstrating the promise of performing vessel morphology analysis using VWI alone.

American Football Position-Specific Neurometabolic Changes in High School Athletes: A Magnetic Resonance Spectroscopic Study.

Reports estimate between 1.6-3.8 million sports-related concussions occur annually, with 30% occurring in youth male American football athletes. Many studies report neurophysiological changes in these athletes, but the exact reasons for these changes remain elusive. Investigation of injury mechanics highlights a need to address how player position might impact these changes. Here, 55 high school American football athletes (20 linemen; 35 non-linemen) underwent magnetic resonance spectroscopy four times over the course of a football season-once prior to the season (Pre), twice during (In1, In2), and once following (Post) to quantify metabolites (N-acetyl aspartate, choline, creatine, myo-inositol, and glutamate/glutamine) in the dorsolateral prefrontal cortex (DLPFC) and primary motor cortex (M1). Head acceleration events (HAEs) were monitored at each practice and game. Spectroscopic and HAE data were analyzed by imaging session and player position. Linear regression analyses were conducted between metabolite levels and HAEs, and metabolite levels in football athletes were compared with age-and gender-matched non-contact athletes. Across-season (i.e., between Pre and In1, In2, Post), different DLPFC and M1 metabolites decreased (p < 0.05) according to player position (i.e., linemen vs. non-linemen). The majority of regression results involved DLPFC metabolites in linemen, where metabolite levels were higher from Pre to Post, with increasing HAE load. Comparisons with control athletes revealed higher metabolite levels in football athletes both before and after the season. This study highlights the importance of player position when conducting analyses on American football athletes and demonstrates elevated DLPFC and M1 brain metabolites in football athletes compared with control athletes at both Pre and Post, suggesting potential HAE-related neurocompensatory mechanisms.

Optimization of the left ventricle ejection fraction estimate obtained during cardiac adenosine stress 82Rubidium-PET scanning: impact of different reconstruction protocols

BackgroundLeft ventricular ejection fraction (LVEF) estimation using adenosine stress myocardial perfusion imaging (MPI) can be challenging. The short half-life of adenosine and the guideline-recommended adenosine infusion stop during Rubidium-82 acquisition protocol may affect the accuracy and repeatability of the LVEF measures. MethodsThis study comprised 25 healthy volunteers (median age 23 years) who underwent repeat myocardial perfusion imaging (MPI) sessions employing Rubidium-82 PET/CT. A guideline-recommended reconstruction protocol was used for both rest and adenosine stress MPI (150-360 s post-radiotracer injection, standardrecon). For the stress MPI protocol, two additional reconstruction protocols were considered; one was employing 60 seconds data (150-210 seconds, shortfixed) and the other a dynamic frame window based on the bolus arrival of Rubidium-82 in the heart until 210 seconds (x-210 seconds, shortindividual). We report rest and stress LVEF, the LVEF reserve, and the LVEF reserve repeatability. ResultsDifferences in the LVEF assessments were observed between the guideline recommended and alternative reconstruction protocol (LVEF stress MPI: standardrecon = 68 ± 7%, shortfixed = 71 ± 7% (P = .08), shortindividual = 72 ± 7% (P = .04)), and the LVEF reserve was reduced for the guideline-recommended protocol (standardrecon = 7.8 ± 3.5, shortfixed = 10.1 ± 3.7, shortindividual = 10.5 ± 3.6, all P < .001). The best repeatability measures were obtained for the shortindividual protocol (repeatability: standardrecon = 45.3%, shortfixed = 41.2%, shortindividual = 31.7%). ConclusionWe recommend using the shortindividual reconstruction protocol for improved LVEF repeatability and reserve assessment. Alternatively, in centers with limited technical support we recommend the use of the shortfixed protocol.

Long-term in vivo imaging of mouse spinal cord through an optically cleared intervertebral window

The spinal cord accounts for the main communication pathway between the brain and the peripheral nervous system. Spinal cord injury is a devastating and largely irreversible neurological trauma, and can result in lifelong disability and paralysis with no available cure. In vivo spinal cord imaging in mouse models without introducing immunological artifacts is critical to understand spinal cord pathology and discover effective treatments. We developed a minimally invasive intervertebral window by retaining the ligamentum flavum to protect the underlying spinal cord. By introducing an optical clearing method, we achieve repeated two-photon fluorescence and stimulated Raman scattering imaging at subcellular resolution with up to 15 imaging sessions over 6–167 days and observe no inflammatory response. Using this optically cleared intervertebral window, we study neuron-glia dynamics following laser axotomy and observe strengthened contact of microglia with the nodes of Ranvier during axonal degeneration. By enabling long-term, repetitive, stable, high-resolution and inflammation-free imaging of mouse spinal cord, our method provides a reliable platform in the research aiming at interpretation of spinal cord physiology and pathology.

Sex Modulates the Pathological Aging Effect on Caudate Functional Connectivity in Mild Cognitive Impairment.

PurposeTo assess the pathological aging effect on caudate functional connectivity among mild cognitive impairment (MCI) participants and examine whether and how sex and amyloid contribute to this process.Materials and MethodsTwo hundred and seventy-seven functional magnetic resonance imaging (fMRI) sessions from 163 cognitive normal (CN) older adults and 309 sessions from 139 participants with MCI were included as the main sample in our analysis. Pearson's correlation was used to characterize the functional connectivity (FC) between caudate nuclei and each brain region, then caudate nodal strength was computed to quantify the overall caudate FC strength. Association analysis between caudate nodal strength and age was carried out in MCI and CN separately using linear mixed effect (LME) model with covariates (education, handedness, sex, Apolipoprotein E4, and intra-subject effect). Analysis of covariance was conducted to investigate sex, amyloid status, and their interaction effects on aging with the fMRI data subset having amyloid status available. LME model was applied to women and men separately within MCI group to evaluate aging effects on caudate nodal strength and each region's connectivity with caudate nuclei. We then evaluated the roles of sex and amyloid status in the associations of neuropsychological scores with age or caudate nodal strength. An independent cohort was used to validate the sex-dependent aging effects in MCI.ResultsThe MCI group had significantly stronger age-related increase of caudate nodal strength compared to the CN group. Analyzing women and men separately revealed that the aging effect on caudate nodal strength among MCI participants was significant only for women (left: P = 6.23 × 10−7, right: P = 3.37 × 10−8), but not for men (P > 0.3 for bilateral caudate nuclei). The aging effects on caudate nodal strength were not significantly mediated by brain amyloid burden. Caudate connectivity with ventral prefrontal cortex substantially contributed to the aging effect on caudate nodal strength in women with MCI. Higher caudate nodal strength is significantly related to worse cognitive performance in women but not in men with MCI.ConclusionSex modulates the pathological aging effects on caudate nodal strength in MCI regardless of amyloid status. Caudate nodal strength may be a sensitive biomarker of pathological aging in women with MCI.

Joint independent component analysis for hypothesizing spatiotemporal relationships between longitudinal gray and white matter changes in preclinical Alzheimer's disease.

Characterizing relationships between gray matter (GM) and white matter (WM) in early Alzheimer's disease (AD) would improve understanding of how and when AD impacts the brain. However, modeling these relationships across brain regions and longitudinally remains a challenge. Thus, we propose extending joint independent component analysis (jICA) into spatiotemporal modeling of regional cortical thickness and WM bundle volumes leveraging multimodal MRI. We jointly characterize these GM and WM features in a normal aging (n=316) and an age- and sex-matched preclinical AD cohort (n=81) at each of two imaging sessions spaced three years apart, training on the normal aging population in cross-validation and interrogating the preclinical AD cohort. We find this joint model identifies reproducible, longitudinal changes in GM and WM between the two imaging sessions and that these changes are associated with preclinical AD and are plausible considering the literature. We compare this joint model to two focused models: (1) GM features at the first session and WM at the second and (2) vice versa. The joint model identifies components that correlate poorly with those from the focused models, suggesting the different models resolve different patterns. We find the strength of association with preclinical AD is improved in the GM to WM model, which supports the hypothesis that medial temporal and frontal thinning precedes volume loss in the uncinate fasciculus and inferior anterior-posterior association fibers. These results suggest that jICA effectively generates spatiotemporal hypotheses about GM and WM in preclinical AD, especially when specific intermodality relationships are considered a priori.