Shift in excitation-inhibition balance underlies perceptual learning of temporal discrimination.

Temporal perceptual learning (TPL) constitutes a unique and profound demonstration of neural plasticity within the brain. Our understanding for the neurometabolic changes associated with TPL on the other hand has been limited in part by the use of traditional fMRI approaches. Since plasticity in the visual cortex has been shown to underlie perceptual learning of visual information, we tested the hypothesis that TPL of an auditory interval involves a similar change in plasticity of the auditory pathway and if so, whether these changes take place in a lower-order sensory-specific brain area such as the primary auditory cortex (A1), or a higher-order modality-independent brain area such as the inferior parietal cortex (IPC). This distinction will inform us of the mechanisms underlying perceptual learning as well as the locus of change as it relates to TPL. In the present study, we took advantage of a new technique: proton magnetic resonance spectroscopy (MRS) in combination with psychophysical measures to provide the first evidence of changes in neurometabolic processing following 5 days of temporal discrimination training. We measured the (E)xcitation-to-(I)nhibition ratio as an index of learning in the right IPC and left A1 while participants learned an auditory two-tone discrimination task. During the first day of training, we found a significant task-related increase in functional E/I ratio within the IPC. While the A1 exhibited the opposite pattern of neurochemical activity, this relationship did not reach statistical significance. After timing performance has reached a plateau, there were no further changes to functional E/I. These findings support the hypothesis that improvements in temporal discrimination relies on neuroplastic changes in the IPC, but it is possible that both areas work synergistically to acquire a temporal interval.

Brain Glutamate Dynamics Predict Positive Agency in Healthy Women: Insights from Combined Application of Pharmacological Challenge, Comprehensive Affective Assessment, and Magnetic Resonance Spectroscopy.

Contributions of brain glutamate (Glu) to conscious emotion are not well understood. Here, we evaluate the relationship of experimentally induced change in neocortical Glu (ΔGlu) and subjective states in well individuals, using combined application of pharmacological challenge, magnetic resonance spectroscopy (MRS), and comprehensive affective assessment. Drug challenge with d-amphetamine (AMP) (20 mg oral), methamphetamine (MA) (Desoxyn, 20 mg oral), and placebo (PBO) was conducted on three separate test days in a within-subjects double blind design. Proton MRS quantified neurometabolites in the right dorsal anterior cingulate cortex 140-150 min post-drug and PBO. Subjective states were assessed at half hour intervals over 5.5 h on each session, yielding 3792 responses per participant (91,008 responses overall, N = 24 participants), with self-reports reduced by principal components analysis (PCA). PCA produced a primary factor score of AMP- and MA-induced positive agency (ΔPA). MRS indicated drug-induced ΔGlu related positively to ΔPA (ΔGluMA r = +0.44, p < 0.05, N = 21), with large effects in females (ΔGluMA r = +0.52, p < 0.05; ΔGluAMP r = +0.61, p < 0.05, N = 11). Subjective states related to ΔGlu included rise in subjective stimulation, vigor, friendliness, elation, positive mood, positive affect (r's = +0.51 to +0.74, p < 0.05), and alleviation of anxiety in females (r = -0.61, p < 0.05, N = 11). These self-reports correlated with ΔGlu to the extent they loaded on ΔPA (r = 0.95 AMP, p = 5 × 10-10; r = 0.63 MA, p = 0.0015, N = 11), indicating the coherence of ΔGlu effects on emotional states. Timing data indicated Glu shaped positive emotion both concurrently and prospectively, with no relationship with pre-MRS emotion (ΔGluAMP r = +0.59 to +0.65, p's < 0.05; ΔGluMA r = +0.53, p < 0.05, N = 11). Together these findings indicate substantive, mechanistic contributions of neocortical Glu to positive agentic states in healthy individuals, which are most readily observed in women. The findings illustrate the promise of combined application of pharmacological challenge, comprehensive affective assessment, and MRS neuroimaging techniques in basic and clinical studies.

Brain Glutamate Dynamics Predict Positive Agency in Healthy Women.

Contributions of brain glutamate to conscious emotion are not well understood. Here we evaluate the relationship of experimentally-induced change in neocortical glutamate (ΔGlu) and subjective states in well individuals. Drug challenge with d-amphetamine (AMP; 20 mg oral), methamphetamine (MA; Desoxyn®, 20 mg oral), and placebo (PBO) was conducted on three separate test days in a within-subjects double blind design. Proton magnetic resonance spectroscopy (MRS) quantified neurometabolites in the right dorsal anterior cingulate cortex (dACC) 140-150 m post-drug and PBO. Subjective states were assessed at half hour intervals over 5.5-hours on each session, yielding 3,792 responses per participant (91,008 responses overall, N=24 participants). Self-reports were reduced by principal components analysis to a single factor score of AMP- and MA-induced Positive Agency (ΔPA) in each participant. We found drug-induced ΔGlu related positively with ΔPA (ΔGluMA r=+.44, p<.05, N=21), with large effects in females (ΔGluMA r=+.52, p<.05; ΔGluAMP r=+.61, p<.05, N=11). States related to ΔGlu in females included rise in subjective stimulation, vigor, friendliness, elation, positive mood, positive affect (r's=+.51 to +.74, p<.05), and alleviation of anxiety (r=-.61, p<.05, N=11). Self-reports correlated with DGlu to the extent they loaded on ΔPA (r=.95 AMP, p=5×10-10; r=.63 MA, p=.0015, N=11), indicating coherence of ΔGlu effects. Timing data indicated Glu shaped emotion both concurrently and prospectively, with no relationship to pre-MRS emotion (ΔGluAMP r=+.59 to +.65, p's<.05; ΔGluMA r=+.53, p<.05, N=11). Together these findings indicate substantive, mechanistic contributions of neocortical Glu to positive agentic states in healthy individuals, most readily observed in women.

Age-related differences in prefrontal glutamate are associated with increased working memory decay that gives the appearance of learning deficits.

The ability to use past experience to effectively guide decision-making declines in older adulthood. Such declines have been theorized to emerge from either impairments of striatal reinforcement learning systems (RL) or impairments of recurrent networks in prefrontal and parietal cortex that support working memory (WM). Distinguishing between these hypotheses has been challenging because either RL or WM could be used to facilitate successful decision-making in typical laboratory tasks. Here we investigated the neurocomputational correlates of age-related decision-making deficits using an RL-WM task to disentangle these mechanisms, a computational model to quantify them, and magnetic resonance spectroscopy to link them to their molecular bases. Our results reveal that task performance is worse in older age, in a manner best explained by working memory deficits, as might be expected if cortical recurrent networks were unable to sustain persistent activity across multiple trials. Consistent with this, we show that older adults had lower levels of prefrontal glutamate, the excitatory neurotransmitter thought to support persistent activity, compared to younger adults. Individuals with the lowest prefrontal glutamate levels displayed the greatest impairments in working memory after controlling for other anatomical and metabolic factors. Together, our results suggest that lower levels of prefrontal glutamate may contribute to failures of working memory systems and impaired decision-making in older adulthood.

Predicting anterior cruciate ligament failure load with T2* relaxometry and machine learning as a prospective imaging biomarker for revision surgery.

Non-invasive methods to document healing anterior cruciate ligament (ACL) structural properties could potentially identify patients at risk for revision surgery. The objective was to evaluate machine learning models to predict ACL failure load from magnetic resonance images (MRI) and to determine if those predictions were related to revision surgery incidence. It was hypothesized that the optimal model would demonstrate a lower mean absolute error (MAE) than the benchmark linear regression model, and that patients with a lower estimated failure load would have higher revision incidence 2 years post-surgery. Support vector machine, random forest, AdaBoost, XGBoost, and linear regression models were trained using MRI T2* relaxometry and ACL tensile testing data from minipigs (n = 65). The lowest MAE model was used to estimate ACL failure load for surgical patients at 9 months post-surgery (n = 46) and dichotomized into low and high score groups via Youden's J statistic to compare revision incidence. Significance was set at alpha = 0.05. The random forest model decreased the failure load MAE by 55% (Wilcoxon signed-rank test: p = 0.01) versus the benchmark. The low score group had a higher revision incidence (21% vs. 5%; Chi-square test: p = 0.09). ACL structural property estimates via MRI may provide a biomarker for clinical decision making.

Automated segmentation of the healed anterior cruciate ligament from T2 * relaxometry MRI scans.

Collagen organization of the anterior cruciate ligament (ACL) can be evaluated using T2 * relaxometry. However, T2 * mapping requires manual image segmentation, which is a time-consuming process and prone to inter- and intra- segmenter variability. Automating segmentation would address these challenges. A model previously trained using Constructive Interference in Steady State (CISS) scans was applied to T2 * segmentation via transfer learning. It was hypothesized that there would be no significant differences in the model's segmentation performance between T2 * and CISS, structural measures versus ground truth manual segmentation, and reliability versus independent and retest manual segmentation. Transfer learning was conducted using 54 T2 * scans of the ACL. Segmentation performance was assessed with Dice coefficient, precision, and sensitivity, and structurally with T2 * value, volume, subvolume proportions, and cross-sectional area. Model performance relative to independent manual segmentation and repeated segmentation by the ground truth segmenter (retest) were evaluated on a random subset. Segmentation performance was analyzed with Mann-Whitney U tests, structural measures with Wilcoxon signed-rank tests, and performance relative to manual segmentation with repeated-measures analysis of variance/Tukey tests (α = 0.05). T2 * segmentation performance was not significantly different from CISS on all measures (p > 0.35). No significant differences were detected in structural measures (p > 0.50). Automatic segmentation performed as well as the retest on all segmentation measures, whereas independent segmentations were lower than retest and/or automatic segmentation (p < 0.023). Structural measures were not significantly different between segmenters. The automatic segmentation model performed as well on the T2 * sequence as on CISS and outperformed independent manual segmentation while performing as well as retest segmentation.

Inter-alpha Inhibitor Proteins Ameliorate Brain Injury and Improve Behavioral Outcomes in a Sex-Dependent Manner After Exposure to Neonatal Hypoxia Ischemia in Newborn and Young Adult Rats.

Hypoxic-ischemic (HI) brain injury is a major contributor to neurodevelopmental morbidities. Inter-alpha inhibitor proteins (IAIPs) have neuroprotective effects on HI-related brain injury in neonatal rats. However, the effects of treatment with IAIPs on sequential behavioral, MRI, and histopathological abnormalities in the young adult brain after treatment with IAIPs in neonates remain to be determined. The objective of this study was to examine the neuroprotective effects of IAIPs at different neurodevelopmental stages from newborn to young adults after exposure of neonates to HI injury. IAIPs were given as 11-sequential 30-mg/kg doses to postnatal (P) day 7-21 rats after right common carotid artery ligation and exposure to 90 min of 8% oxygen. The resulting brain edema and injury were examined by T2-weighted magnetic resonance imaging (MRI) and cresyl violet staining, respectively. The mean T2 values of the ipsilateral hemisphere from MRI slices 6 to 10 were reduced in IAIP-treated HI males + females on P8, P9, and P10 and females on P8, P9, P10, and P14. IAIP treatment reduced hemispheric volume atrophy by 44.5 ± 29.7% in adult male + female P42 rats and improved general locomotor abilities measured by the righting reflex over time at P7.5, P8, and P9 in males + females and males and muscle strength/endurance measured by wire hang on P16 in males + females and females. IAIPs provided beneficial effects during the learning phase of the Morris water maze with females exhibiting beneficial effects. IAIPs confer neuroprotection from HI-related brain injury in neonates and even in adult rats and beneficial MRI and behavioral benefits in a sex-dependent manner.

Reproducibility and postacquisition correction methods for quantitative magnetic resonance imaging of the anterior cruciate ligament (ACL).

Quantitative magnetic resonance imaging has been used to evaluate the structural integrity of knee joint structures. However, variations in acquisition parameters between scanners pose significant challenges. Understanding the effect of small differences in acquisition parameters for quantitative sequences is vital to the validity of cross-institutional studies, and for the harmonization of large, heterogeneous datasets to train machine learning models. The study objective was to assess the reproducibility of T2 * relaxometry and the constructive interference in steady-state sequence (CISS) across scanners, with minimal hardware-necessitated changes to acquisition parameters. It was hypothesized that there would be no significant differences between scanners in anterior cruciate ligament T2 * relaxation times and CISS signal intensities (SI). Secondarily, it was hypothesized that differences could be corrected by rescaling the SI distribution to harmonize between scanners. Seven volunteers were scanned on 3T Prisma and Tim Trio scanners (Siemens). Three correction methods were evaluated for T2 *: inverse echo time scaling, z-scoring, and Nyúl histogram matching. For CISS, scans were normalized to cortical bone, scaled by the background noise ratio, and log-transformed. Before correction, significant mean differences of 6.0 ± 3.2 ms (71.8%; p = 0.02) and 0.49 ± 0.15 units (40.7%; p = 0.02) for T2 * and CISS across scanners were observed, respectively. After rescaling, T2 * differences decreased to 2.6 ± 2.7 ms (23.9%; p = 0.03), 1.3 ± 2.5 ms (10.9%; p = 0.13), and 1.27 ± 3.0 ms (19.6%; p = 0.40) for inverse echo time, z-scoring, and Nyúl, respectively, while CISS decreased to 0.01 ± 0.11 units (4.0%; p = 0.87). These findings suggest that small acquisition parameter differences may lead to large changes in T2 * and SI values that must be reconciled to compare data across magnets.

The neurobiology of wellness: 1H-MRS correlates of agency, flexibility and neuroaffective reserves in healthy young adults.

Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive imaging technique that measures the concentration of metabolites in defined areas of the human brain in vivo. The underlying structure of natural metabolism-emotion relationships is unknown. Further, there is a wide range of between-person differences in metabolite concentration in healthy individuals, but the significance of this variation for understanding emotion in healthy humans is unclear. Here we investigated the relationship of two emotional constructs, agency and flexibility, with the metabolites glutamate and glutamine (Glx), N-acetylaspartate (tNAA), choline (Cho), creatine (tCr), and myo-inositol (Ins) in the right dorsal anterior cingulate cortex (dACC) in medically and psychiatrically healthy volunteers (N = 20, 9 female; mean age = 22.8 years, SD = 3.40). The dACC was selected because this region is an integrative hub involved in multiple brain networks of emotion, cognition and behavior. Emotional traits were assessed using the Multidimensional Personality Questionnaire Brief Form (MPQ-BF), an empirically derived self-report instrument with an orthogonal factor structure. Phenotypes evaluated were positive and negative agency (MPQ-BF Social Potency, Aggression), emotional and behavioral flexibility (MPQ-BF Absorption, Control-reversed), and positive and negative affect (MPQ-BF Social Closeness; Stress Reaction, Alienation). The resting concentration of tNAA in the dACC was robustly positively correlated with Absorption (r = +0.56, unadjusted p = .005), moderately positively correlated with Social Potency (r = +0.42, unadjusted p = .03), and robustly negatively correlated with Aggression (r = -0.59, unadjusted p = .003). Absorption and Aggression accounted for substantial variance in tNAA (R2 = 0.31, 0.35; combined R2 = 0.50), and survived correction for multiple comparisons (Holm-Bonferroni adjusted p = .032, 0.021, respectively). dACC Glx and Cho had modest relationships with behavioral flexibility and social affiliation that did not survive this multiple correction, providing effect sizes for future work. Principal Component Analysis (PCA) revealed a three-factor orthogonal solution indicating specific relationships between: 1) Glx and behavioral engagement; 2) Cho and affiliative bonding; and 3) tNAA and a novel dimension that we term neuroaffective reserves. Our results inform the neurobiology of agency and flexibility and lay the groundwork for understanding mechanisms of natural emotion using 1H-MRS.

Adjuvant Thermal Accelerant Gel Use Increases Microwave Ablation Zone Temperature in Porcine Liver as Measured by MR Thermometry.

PURPOSE: To determine the effects of a thermal accelerant gel on temperature parameters during microwave liver ablation. MATERIALS AND METHODS: Sixteen consecutive liver ablations were performed in 5 domestic swine under general anesthesia with (n = 8) and without (n = 8) administration of thermal accelerant gel. Ablation zone temperature was assessed by real-time MR thermometry, measured as maximum temperature (Tmax) and the volume of tissue ≥ 60°C (V60). Tissue heating rate, ablation zone shape, and thermal energy deposition using the temperature degree-minutes at 43°C (TDM43) index were also measured. Differences between groups were analyzed using generalized mixed modeling with significance set at P = .05. RESULTS: Mean peak ablation zone temperature was significantly greater with thermal accelerant use (mean Tmax, thermal accelerant: 120.0°C, 95% confidence interval [CI] 113.0°C-126.9°C; mean Tmax, control: 80.3°C, 95% CI 72.7°C-88.0°C; P < .001), and a significantly larger volume of liver tissue achieved or exceeded 60°C when thermal accelerant was administered (mean V60, thermal accelerant: 22.2 cm3; mean V60, control: 15.9 cm3; P < .001). Significantly greater thermal energy deposition was observed during ablations performed with accelerant (mean TDM43, thermal accelerant: 198.4 min, 95% CI 170.7-230.6 min; mean TDM43, control: 82.8 min, 95% CI 80.5-85.1 min; P < .0001). The rate of tissue heating was significantly greater with thermal accelerant use (thermal accelerant: 5.8 min ± 0.4; control: 10.0 min; P < .001), and accelerant gel ablations demonstrated a more spherical temperature distribution (P = .002). CONCLUSIONS: Thermal accelerant use is associated with higher microwave ablation zone temperatures, greater thermal energy deposition, and faster and more spherical tissue heating compared with control ablations.

Psychostimulant drug effects on glutamate, Glx, and creatine in the anterior cingulate cortex and subjective response in healthy humans.

Prescription psychostimulants produce rapid changes in mood, energy, and attention. These drugs are widely used and abused. However, their effects in human neocortex on glutamate and glutamine (pooled as Glx), and key neurometabolites such as N-acetylaspartate (tNAA), creatine (tCr), choline (Cho), and myo-inositol (Ins) are poorly understood. Changes in these compounds could inform the mechanism of action of psychostimulant drugs and their abuse potential in humans. We investigated the acute impact of two FDA-approved psychostimulant drugs on neurometabolites using magnetic resonance spectroscopy (1H MRS). Single clinically relevant doses of d-amphetamine (AMP, 20 mg oral), methamphetamine (MA, 20 mg oral; Desoxyn®), or placebo were administered to healthy participants (n = 26) on three separate test days in a placebo-controlled, double-blinded, within-subjects crossover design. Each participant experienced all three conditions and thus served as his/her own control. 1H MRS was conducted in the dorsal anterior cingulate cortex (dACC), an integrative neocortical hub, during the peak period of drug responses (140-150 m post ingestion). D-amphetamine increased the level of Glu (p = .0001), Glx (p = .003), and tCr (p = .0067) in the dACC. Methamphetamine increased Glu in females, producing a significant crossover interaction pattern with gender (p = .02). Drug effects on Glu, tCr, and Glx were positively correlated with subjective drug responses, predicting both the duration of AMP liking (Glu: r = +.49, p = .02; tCr: r = +.41, p = .047) and the magnitude of peak drug high to MA (Glu: r = +.52, p = .016; Glx: r = +.42, p = .049). Neither drug affected the levels of tNAA, Cho, or Ins after correction for multiple comparisons. We conclude that d-amphetamine increased the concentration of glutamate, Glx, and tCr in the dACC in male and female volunteers 21/2 hours after drug consumption. There was evidence that methamphetamine differentially affects dACC Glu levels in women and men. These findings provide the first experimental evidence that specific psychostimulants increase the level of glutamatergic compounds in the human brain, and that glutamatergic changes predict the extent and magnitude of subjective responses to psychostimulants.

Magnetic resonance measurements of tissue quantity and quality using T2 * relaxometry predict temporal changes in the biomechanical properties of the healing ACL.

The purpose of this study was to develop a magnetic resonance T2 * relaxometry-based multiple linear regression model to predict the structural properties of the healing anterior cruciate ligament (ACL) over a 24-week healing period following ACL repair in Yucatan minipigs. Two hypotheses were tested: (i) that a regression model based on ACL sub-volumes containing short and long T2 * relaxation times would outperform a competing model based on sub-volumes of short T2 * relaxation times only; and (ii) that an optimized regression model would be capable of predicting ACL structural properties between 6 and 24 weeks post-repair. ACLs were imaged in 24 minipigs (8/group) at either 6, 12, or 24 weeks after ACL repair. The structural properties of the ACLs were determined from tensile failure tests. Four multiple linear regression models of increasing complexity were fitted to the data. Akaike Information Criterion values and Bland-Altman tests were used to compare model performance and to test the hypotheses. The structural properties predicted from the multiple linear regression model that was based on the change in ACL sub-volumes of both the short and long T2 * relaxation times over the healing period were in closest agreement to the measured values, suggesting that the amounts of both organized and disorganized collagen, and the change in these quantities over time, are required to predict the structural properties of healing ACLs accurately. CLINICAL SIGNIFICANCE: our time-specific, T2 *-based regression model may allow us to estimate the structural properties of ACL repairs in vivo longitudinally. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1701-1709, 2018.

Sensitivity of ACL volume and T2∗ relaxation time to magnetic resonance imaging scan conditions.

Anterior cruciate ligament (ACL) volume and T2∗ relaxation times from magnetic resonance (MR) images have been previously shown to predict the structural properties of healing ligaments. We investigated whether MR imaging scan resolution and condition (in vivo, in situ, or ex vivo) affected ACL volume and T2∗ relaxation times in intact ligaments. ACLs of 14 pigs were imaged using a 3T scanner and a six-channel flexcoil using at least two of four possible scan conditions: (1) in vivo moderate resolution (n=14); (2) in vivo high resolution (n=7); (3) in situ high resolution acquired within 60 minutes of euthanasia (n=6); and (4) ex vivo high resolution following hind limb disarticulation and one freeze-thaw cycle (n=7). T2∗ relaxation times were mapped to the ACL voxels. The total ACL volume was then divided into four sub-volumes (Vol1-4) based on predetermined increasing ranges of T2∗ times. ACL T2∗ statistics (first quartile, median, and standard deviation (SD)) were computed. Scan resolution had no effect on the total ACL volume, but Vol1 and first quartile T2∗ times decreased with high resolution and in situ/ex vivo scan conditions. The most dramatic differences in T2∗ summary statistics were between in vivo moderate and ex vivo high resolution scan conditions that included a freeze-thaw cycle: ACL T2∗ SD increased by over 50% in 9 animals, and more than 90% in 4 animals. Our results indicated that T2∗-based prediction models to quantify in vivo structural properties of healing ligaments should be based on high resolution in vivo MR scan conditions.

Overlearning hyperstabilizes a skill by rapidly making neurochemical processing inhibitory-dominant.

Overlearning refers to the continued training of a skill after performance improvement has plateaued. Whether overlearning is beneficial is a question in our daily lives that has never been clearly answered. Here we report a new important role: overlearning in humans abruptly changes neurochemical processing, to hyperstabilize and protect trained perceptual learning from subsequent new learning. Usually, learning immediately after training is so unstable that it can be disrupted by subsequent new learning until after passive stabilization occurs hours later. However, overlearning so rapidly and strongly stabilizes the learning state that it not only becomes resilient against, but also disrupts, subsequent new learning. Such hyperstabilization is associated with an abrupt shift from glutamate-dominant excitatory to GABA-dominant inhibitory processing in early visual areas. Hyperstabilization contrasts with passive and slower stabilization, which is associated with a mere reduction of excitatory dominance to baseline levels. Using hyperstabilization may lead to efficient learning paradigms.

T2* relaxometry and volume predict semi-quantitative histological scoring of an ACL bridge-enhanced primary repair in a porcine model.

Magnetic resonance imaging (MRI) variables, such as T2* and volume, can predict the healing ligament structural properties. How these MR variables relate to semi-quantitative histology of the healing ACL is yet unknown. We hypothesized that T2* and volume would predict the histological scoring of a healing ACL. Yucatan minipigs underwent ACL transection and received bridge-enhanced ACL repair or no treatment. The surgical legs were harvested after 52 weeks and imaged using a high resolution 2-echo sequence. For each ligament, the volume and median T2* values were determined. The ACL specimens were then histologically analyzed using the advanced Ligament Maturity Index (LMI). The T2* of the healing ligaments significantly predicted the total LMI score as well as the cell, collagen and vessel sub-scores; R(2) = 0.78, 0.67, 0.65, and 0.60, respectively (p ≤ 0.001). The ligament volume also predicted the total LMI score, cell, and collagen sub-scores; R(2) = 0.39, 0.33, 0.37, and 0.60, respectively (p ≤ 0.001). A lower ligament T2* or a higher volume was associated with higher histological scores of the healing ligaments. This study provides a critical step in the development of a non-invasive method to evaluate ligament healing on a microscopic scale.

A highly sensitive x-ray imaging modality for hepatocellular carcinoma detection in vitro.

Innovations that improve sensitivity and reduce cost are of paramount importance in diagnostic imaging. The novel x-ray imaging modality called spatial frequency heterodyne imaging (SFHI) is based on a linear arrangement of x-ray source, tissue, and x-ray detector, much like that of a conventional x-ray imaging apparatus. However, SFHI rests on a complete paradigm reversal compared to conventional x-ray absorption-based radiology: while scattered x-rays are carefully rejected in absorption-based x-ray radiology to enhance the image contrast, SFHI forms images exclusively from x-rays scattered by the tissue. In this study we use numerical processing to produce x-ray scatter images of hepatocellular carcinoma labeled with a nanoparticle contrast agent. We subsequently compare the sensitivity of SFHI in this application to that of both conventional x-ray imaging and magnetic resonance imaging (MRI). Although SFHI is still in the early stages of its development, our results show that the sensitivity of SFHI is an order of magnitude greater than that of absorption-based x-ray imaging and approximately equal to that of MRI. As x-ray imaging modalities typically have lower installation and service costs compared to MRI, SFHI could become a cost effective alternative to MRI, particularly in areas of the world with inadequate availability of MRI facilities.

The synergistic effects of anxiety and cerebral hypoperfusion on cognitive dysfunction in older adults with cardiovascular disease.

OBJECTIVES: Anxiety is a risk factor for cardiovascular disease (CVD) and is associated with neurocognitive outcomes. The effect of anxiety on brain perfusion in a CVD population has yet to be examined, and no study has investigated the interactive effects of anxiety and cerebral perfusion on cognition. METHODS: A total of 55 older adults with CVD completed the Beck Anxiety Inventory (BAI) and underwent arterial spin labeling to quantify cortical perfusion and thickness. Participants were administered the Mini-Mental State Examination (MMSE) and the Repeatable Battery for the Assessment of Neuropsychological Status. RESULTS: Reduced perfusion predicted poorer cognition and decreased cortical thickness. Higher anxiety score predicted worse memory performance and decreased frontal perfusion. Frontal lobe hypoperfusion combined with increased BAI scores exacerbated poorer MMSE performance. CONCLUSIONS: Higher anxiety may exacerbate the effects of cerebral hypoperfusion on cognitive impairment. Longitudinal studies are needed to confirm our findings and determine whether anxiety treatment improves neurocognitive outcomes in CVD.

The impact of hypertension on cerebral perfusion and cortical thickness in older adults.

Hypertension may increase risk for dementia possibly because of its association with decreased cortical thickness. Disturbed cerebral autoregulation is one plausible mechanism by which hypertension impacts the cerebral structure, but the associations among hypertension, brain perfusion, and cortical thickness are poorly understood. The current sample consisted of 58 older adults with varying levels of vascular disease. Diagnostic history of hypertension and antihypertensive medication status was ascertained through self-report, and when available, confirmed by medical record review. All participants underwent arterial spin labeling and T1-weighted magnetic resonance imaging to quantify total and regional cortical perfusion and thickness. Analysis of covariance adjusting for medical variables showed that participants with hypertension exhibited reduced temporal and occipital brain perfusion and total and regional cortical thickness relative to those without hypertension. The effects of hypertension on total brain perfusion remained unchanged even after adjustment for age, although no such pattern emerged for cortical thickness. Decreased total brain perfusion predicted reduced thickness of the total brain and of the frontal, temporal, and parietal lobe cortices. Antihypertensive treatment was not associated with total cerebral perfusion or cortical thickness. This study provides initial evidence for the adverse effects of a diagnostic history of hypertension on brain hypoperfusion and reduced cortical thickness. Longitudinal studies are needed to investigate the role of hypertension and its interaction with other contributing factors (e.g., age) in the manifestation of cerebral hypoperfusion and reduced cortical thickness.