Development of the Split-Bolus Pulmonary Arteriovenous Separating Computed Tomography Angiography Protocol Based on Time Enhancement Curve for Lung Cancer Surgery.

OBJECTIVE: We devised a split-bolus injection and imaging protocol for pulmonary artery and vein separation computed tomography (CT) angiography based on time enhancement curve characterization. Furthermore, we aimed to evaluate the contrast enhancement effect and success rate of blood vessel separation between the pulmonary artery and vein of this proposed protocol. METHODS: In this study, 102 patients (45 patients with the standard protocol and 57 patients with the proposed protocol) who underwent pulmonary arteriovenous computed tomography angiography were included. The CT values of various vessels, CT value difference between the pulmonary trunk and left atrium, and coefficient of variation in pulmonary arteries and veins were obtained from images of the standard and proposed protocols. RESULTS: The CT values in the proposed protocol for the pulmonary trunk were significantly higher than those in the standard protocol (487.3 [415.5-546.9] HU vs. 293.0 [259.0-350.0] HU, P < 0.01). The CT value difference between the pulmonary trunk and left atrium in the proposed protocol was significantly higher than that in the conventional protocol (211.3 [158.0-265.7] HU vs. 32 [-30.0-55.0] HU, P < 0.01). The coefficient of variation in the proposed protocol was 0.08 (0.06-0.10) and 0.09 (0.08-0.11) in pulmonary arteries and 0.08 (0.06-0.09) and 0.09 (0.07-0.12) in pulmonary veins, respectively. CONCLUSIONS: The proposed protocol achieved separation between the pulmonary artery and vein in many patients, making it useful for the preoperative assessment of individual thoracic anatomy.

Delineation of the internal iliac vein using MRI with true FISP sequence in patients with locally recurrent rectal cancer: A pilot study using CT/MRI fusion.

PURPOSE: This study assessed the feasibility of using three-dimensional (3D) models of intrapelvic vascular patterns constructed using computed tomography (CT) and magnetic resonance imaging (MRI) fusion data for preoperative planning in patients with locally recurrent rectal cancer. METHODS: Eleven patients scheduled for pelvic exenteration were included. The 3D fusion data of the intrapelvic vessels constructed using CT and MRI with true fast imaging with steady-state precession sequence (True FISP) were evaluated preoperatively. Contrast ratios (CR) between the piriformis muscle and the intrapelvic vessels were calculated to identify a valid modality for 3D modeling and creating CT/MRI fusion-reconstructed volume-rendered images. RESULTS: The CR values of the internal and external iliac arteries were significantly higher on CT images than MR images (CT vs. MRI; 0.63 vs. 0.45, p < 0.01). However, the CR value of the internal iliac vein was significantly higher on MR than CT images (CT vs. MRI; 0.23 vs. 0.55, p < 0.01). CONCLUSIONS: MRI with True FISP yielded high signal-to-noise ratios and aided in delineating the internal iliac vein around the piriformis muscle. More precise 3D models can be constructed using this technique in the future to aid in the resection of locally recurrent rectal cancer.

Time course of recovery of different motor functions following a reproducible cortical infarction in non-human primates.

A major challenge in human stroke research is interpatient variability in the extent of sensorimotor deficits and determining the time course of recovery following stroke. Although the relationship between the extent of the lesion and the degree of sensorimotor deficits is well established, the factors determining the speed of recovery remain uncertain. To test these experimentally, we created a cortical lesion over the motor cortex using a reproducible approach in four common marmosets, and characterized the time course of recovery by systematically applying several behavioral tests before and up to 8 weeks after creation of the lesion. Evaluation of in-cage behavior and reach-to-grasp movement revealed consistent motor impairments across the animals. In particular, performance in reaching and grasping movements continued to deteriorate until 4 weeks after creation of the lesion. We also found consistent time courses of recovery across animals for in-cage and grasping movements. For example, in all animals, the score for in-cage behaviors showed full recovery at 3 weeks after creation of the lesion, and the performance of grasping movement partially recovered from 4 to 8 weeks. In addition, we observed longer time courses of recovery for reaching movement, which may rely more on cortically initiated control in this species. These results suggest that different recovery speeds for each movement could be influenced by what extent the cortical control is required to properly execute each movement.

Motility Profile of Captive-Bred Marmosets Revealed by a Long-Term In-Cage Monitoring System.

A quantitative evaluation of motility is crucial for studies employing experimental animals. Here, we describe the development of an in-cage motility monitoring method for new world monkeys using off-the-shelf components, and demonstrate its capability for long-term operation (e.g., a year). Based on this novel system, we characterized the motility of the common marmoset over different time scales (seconds, hours, days, and weeks). Monitoring of seven young animals belonging to two different age groups (sub-adult and young-adult) over a 231-day period revealed: (1) strictly diurnal activity (97.3% of movement during daytime), (2) short-cycle (∼20 s) transition in activity, and (3) bimodal diurnal activity including a "siesta" break. Additionally, while the mean duration of short-cycle activity, net daily activity, and diurnal activity changed over the course of development, 24-h periodicity remained constant. Finally, the method allowed for detection of progressive motility deterioration in a transgenic marmoset. Motility measurement offers a convenient way to characterize developmental and pathological changes in animals, as well as an economical and labor-free means for long-term evaluation in a wide range of basic and translational studies.

Decoding of muscle activity from the sensorimotor cortex in freely behaving monkeys.

Remarkable advances have recently been made in the development of Brain-Machine Interface (BMI) technologies for restoring or enhancing motor function. However, the application of these technologies may be limited to patients in static conditions, as these developments have been largely based on studies of animals (e.g., non-human primates) in constrained movement conditions. The ultimate goal of BMI technology is to enable individuals to move their bodies naturally or control external devices without physical constraints. Here, we demonstrate accurate decoding of muscle activity from electrocorticogram (ECoG) signals in unrestrained, freely behaving monkeys. We recorded ECoG signals from the sensorimotor cortex as well as electromyogram signals from multiple muscles in the upper arm while monkeys performed two types of movements with no physical restraints, as follows: forced forelimb movement (lever-pull task) and natural whole-body movement (free movement within the cage). As in previous reports using restrained monkeys, we confirmed that muscle activity during forced forelimb movement was accurately predicted from simultaneously recorded ECoG data. More importantly, we demonstrated that accurate prediction of muscle activity from ECoG data was possible in monkeys performing natural whole-body movement. We found that high-gamma activity in the primary motor cortex primarily contributed to the prediction of muscle activity during natural whole-body movement as well as forced forelimb movement. In contrast, the contribution of high-gamma activity in the premotor and primary somatosensory cortices was significantly larger during natural whole-body movement. Thus, activity in a larger area of the sensorimotor cortex was needed to predict muscle activity during natural whole-body movement. Furthermore, decoding models obtained from forced forelimb movement could not be generalized to natural whole-body movement, which suggests that decoders should be built individually and according to different behavior types. These results contribute to the future application of BMI systems in unrestrained individuals.

Double Virus Vector Infection to the Prefrontal Network of the Macaque Brain.

To precisely understand how higher cognitive functions are implemented in the prefrontal network of the brain, optogenetic and pharmacogenetic methods to manipulate the signal transmission of a specific neural pathway are required. The application of these methods, however, has been mostly restricted to animals other than the primate, which is the best animal model to investigate higher cognitive functions. In this study, we used a double viral vector infection method in the prefrontal network of the macaque brain. This enabled us to express specific constructs into specific neurons that constitute a target pathway without use of germline genetic manipulation. The double-infection technique utilizes two different virus vectors in two monosynaptically connected areas. One is a vector which can locally infect cell bodies of projection neurons (local vector) and the other can retrogradely infect from axon terminals of the same projection neurons (retrograde vector). The retrograde vector incorporates the sequence which encodes Cre recombinase and the local vector incorporates the "Cre-On" FLEX double-floxed sequence in which a reporter protein (mCherry) was encoded. mCherry thus came to be expressed only in doubly infected projection neurons with these vectors. We applied this method to two macaque monkeys and targeted two different pathways in the prefrontal network: The pathway from the lateral prefrontal cortex to the caudate nucleus and the pathway from the lateral prefrontal cortex to the frontal eye field. As a result, mCherry-positive cells were observed in the lateral prefrontal cortex in all of the four injected hemispheres, indicating that the double virus vector transfection is workable in the prefrontal network of the macaque brain.

Functional differences between macaque prefrontal cortex and caudate nucleus during eye movements with and without reward.

The prefrontal cortex and the basal ganglia form mutually connected networks and are thought to play essential roles together in guiding goal-directed behaviors. Yet, these structures seem to have independent pathways to motor outputs as well, suggesting differential contributions to goal-directed behaviors. We hypothesized that the prefrontal cortex guides actions to a direction required by external demands and the basal ganglia guide actions to an internally motivated direction. To test this hypothesis, we used a task in which monkeys were required to make a memory-guided saccade to a direction indicated by a visual cue while only one direction was associated with reward. We observed a functional dissociation between the lateral prefrontal cortex (LPFC), which commonly represented the cue direction, and the caudate nucleus (CD), which commonly represented the reward-associated direction. Furthermore, cue-directed and reward-directed signals were integrated differently in the two areas; when the cue direction and the reward direction were opposite, LPFC neurons maintained tuning to the cue direction, whereas CD neurons lost the tuning. Different types of spatial tuning in the two brain areas may contribute to different types of goal-directed behavior.

Influence of reward expectation on visuospatial processing in macaque lateral prefrontal cortex.

The lateral prefrontal cortex (LPFC) has been implicated in visuospatial processing, especially when it is required to hold spatial information during a delay period. It has also been reported that the LPFC receives information about expected reward outcome. However, the interaction between visuospatial processing and reward processing is still unclear because the two types of processing could not be dissociated in conventional delayed response tasks. To examine this, we used a memory-guided saccade task with an asymmetric reward schedule and recorded 228 LPFC neurons. The position of the target cue indicated the spatial location for the following saccade and the color of the target cue indicated the reward outcome for a correct saccade. Activity of LPFC was classified into three main types: S-type activity carried only spatial signals, R-type activity carried only reward signals, and SR-type activity carried both. Therefore only SR-type cells were potentially involved in both visuospatial processing and reward processing. SR-type activity was enhanced (SR+) or depressed (SR-) by the reward expectation. The spatial discriminability as expressed by the transmitted information was improved by reward expectation in SR+ type. In contrast, when reward information was coded by an increase of activity in the reward-absent condition (SR- type), it did not improve the spatial representation. This activity appeared to be involved in gaze fixation. These results extend previous findings suggesting that the LPFC exerts dual influences based on predicted reward outcome: improvement of memory-guided saccades (when reward is expected) and suppression of inappropriate behavior (when reward is not expected).

Feature-based anticipation of cues that predict reward in monkey caudate nucleus.

A subset of caudate neurons fires before cues that instruct the monkey what he should do. To test the hypothesis that the anticipatory activity of such neurons depends on the context of stimulus-reward mapping, we examined their activity while the monkeys performed a memory-guided saccade task in which either the position or the color of a cue indicated presence or absence of reward. Some neurons showed anticipatory activity only when a particular position was associated with reward, while others fired selectively for color-reward associations. The functional segregation suggests that caudate neurons participate in feature-based anticipation of visual information that predicts reward. This neuronal code influences the general activity level in response to visual features without improving the quality of visual discrimination.