In vivo functional brain mapping using ultra-high-field fMRI in awake common marmosets.

The common marmoset (Callithrix jacchus) is gaining attention in the field of cognitive neuroscience. The development of an effective protocol for fMRI data acquisition in awake marmosets is a key factor in developing reliable comparative studies. Here, we describe a protocol to obtain fMRI data in awake marmosets using auditory and visual stimulation. We describe steps for surgical and anesthesia procedures, MRI training, and positioning the marmosets within an MRI-compatible body restraint. We then detail fMRI scanning and preprocessing of functional images. For complete details on the use and execution of this protocol, please refer to Jafari et al. (2023).1.

A radiofrequency coil to facilitate task-based fMRI of awake marmosets.

BACKGROUND: The small common marmoset (Callithrix jacchus) is an ideal nonhuman primate for awake fMRI in ultra-high field small animal MRI scanners. However, it can often be challenging in task-based fMRI experiments to provide a robust stimulus within the MRI environment while using hardware (an RF coil and restraint system) that is compatible with awake imaging. NEW METHOD: Here we present an RF coil and restraint system that permits unimpeded access to an awake marmoset's head subsequent to immobilization, thereby permitting the setup of peripheral devices and stimuli proximal to the head. RESULTS: As an example application, an fMRI experiment probing whole-brain activation in response to marmoset vocalizations was conducted-this paradigm showed significant bilateral activation in the inferior colliculus, medial lateral geniculate nucleus, and auditory cortex. COMPARISON WITH EXISTING METHOD(S): The coil performance was evaluated and compared to a previously published restraint system with integrated RF coil. The image and temporal SNR were improved by up to 58 % and 27 %, respectively, in the peripheral cortex and by 30 % and 3 % in the centre of the brain. The restraint-system topology limited head motion to less than 100 µm of translation and 0.30° of rotation when measured over a 15-minute acquisition. CONCLUSIONS: The proposed hardware solution provides a versatile approach to awake-marmoset imaging and, as demonstrated, can facilitate task-based fMRI.

Simultaneous functional MRI of two awake marmosets.

Social cognition is a dynamic process that requires the perception and integration of a complex set of idiosyncratic features between interacting conspecifics. Here we present a method for simultaneously measuring the whole-brain activation of two socially interacting marmoset monkeys using functional magnetic resonance imaging. MRI hardware (a radiofrequency coil and peripheral devices) and image-processing pipelines were developed to assess brain responses to socialization, both on an intra-brain and inter-brain level. Notably, the brain activation of a marmoset when viewing a second marmoset in-person versus when viewing a pre-recorded video of the same marmoset-i.e., when either capable or incapable of socially interacting with a visible conspecific-demonstrates increased activation in the face-patch network. This method enables a wide range of possibilities for potentially studying social function and dysfunction in a non-human primate model.

Radiofrequency coil for routine ultra-high-field imaging with an unobstructed visual field.

Many neuroscience applications have adopted functional MRI as a tool to investigate the healthy and diseased brain during the completion of a task. While ultra-high-field MRI has allowed for improved contrast and signal-to-noise ratios during functional MRI studies, it remains a challenge to create local radiofrequency coils that can accommodate an unobstructed visual field and be suitable for routine use, while at the same time not compromise performance. Performance (both during transmission and reception) can be improved by using close-fitting coils; however, maintaining sensitivity over the whole brain often requires the introduction of coil elements proximal to the eyes, thereby partially occluding the subject's visual field. This study presents a 7 T head coil, with eight transmit dipoles and 32 receive loops, that is designed to remove visual obstructions from the subject's line of sight, allowing for an unencumbered view of visual stimuli, the reduction of anxiety induced from small enclosures, and the potential for eye-tracking measurements. The coil provides a practical solution for routine imaging, including a split design (anterior and posterior halves) that facilitates subject positioning, including those with impaired mobility, and the placement of devices required for patient comfort and motion reduction. The transmit and receive coils displayed no degradation of performance due to adaptions to the design topology (both mechanical and electrical) required to create an unobstructed visual field. All computer-aided design files, electromagnetic simulation models, transmit field maps and local specific absorption rate matrices are provided to promote reproduction.

Reproducibility of Neurite Orientation Dispersion and Density Imaging (NODDI) in rats at 9.4 Tesla.

PURPOSE: Neurite Orientation Dispersion and Density Imaging (NODDI) is a diffusion MRI (dMRI) technique used to characterize tissue microstructure by compartmental modelling of neural water fractions. Intra-neurite, extra-neurite, and cerebral spinal fluid volume fractions are measured. The purpose of this study was to determine the reproducibility of NODDI in the rat brain at 9.4 Tesla. METHODS: Eight data sets were successfully acquired on adult male Sprague Dawley rats. Each rat was scanned twice on a 9.4T Agilent MRI with a 7 ± 1 day separation between scans. A multi-shell diffusion protocol was implemented consisting of 108 total directions varied over two shells (b-values of 1000 s/mm2 and 2000 s/mm2). Three techniques were used to analyze the NODDI scalar maps: mean region of interest (ROI) analysis, whole brain voxel-wise analysis, and targeted ROI analyses (voxel-wise within a given ROI). The coefficient of variation (CV) was used to assess the reproducibility of NODDI and provide insight into necessary sample sizes and minimum detectable effect size. RESULTS: CV maps for orientation dispersion index (ODI) and neurite density index (NDI) showed high reproducibility both between and within subjects. Furthermore, it was found that small biological changes (<5%) may be detected with feasible sample sizes (n < 6-10). In contrast, isotropic volume fraction (IsoVF) was found to have low reproducibility, requiring very large sample sizes (n > 50) for biological changes to be detected. CONCLUSIONS: The ODI and NDI measured by NODDI in the rat brain at 9.4T are highly reproducible and may be sensitive to subtle changes in tissue microstructure.

Concentric radiofrequency arrays to increase the statistical power of resting-state maps in monkeys.

The close homology of monkeys and humans has increased the prevalence of non-human-primate models in functional MRI studies of brain connectivity. To improve upon the attainable resolution in functional MRI studies, a commensurate increase in the sensitivity of the radiofrequency receiver coil is required to avoid a reduction in the statistical power of the analysis. Most receive coils are comprised of multiple loops distributed equidistantly over a surface to produce spatially independent sensitivity profiles. A larger number of smaller elements will in turn provide a higher signal-to-noise ratio (SNR) over the same field of view. As the loops become physically smaller, noise originating from the sample is reduced relative to noise originating from the coil. In this coil-noise-dominated regime, coil elements can have overlapping sensitivity profiles, yet still possess only mildly correlated noise. In this manuscript, we demonstrate that inductively decoupled, concentric coil arrays can improve temporal SNR when operating in the coil-noise-dominated regime-in contrast to what is expected for the more ubiquitous sample-noise-dominated array. A small, thin, 7-channel flexible coil is developed and operated in conjunction with an existing whole-head monkey coil. The mean and maximum noise correlation between the two arrays was 5% and 23%, respectively. When the flex coil was placed over the sensorimotor cortex, the temporal SNR improved by up to 2.3-fold in the peripheral cortex and up to 1.3-fold at a 2- to 3-cm depth within the brain. When the flex coil was placed over the frontal eye fields, resting-state maps showed substantially elevated sensitivity to correlations in the prefrontal cortex (54%), supplementary eye fields (39%), and anterior cingulate cortex (41%). The concentric-coil topology provided a pragmatic and robust means to significantly improve local temporal SNR and the statistical power of functional connectivity maps.

A geometrically adjustable receive array for imaging marmoset cohorts.

The common marmoset (Callithrix jacchus) is an increasingly popular animal model for translational neuroscience studies, during which anatomical and functional MRI can be useful investigative tools. To attain the requisite SNR for high-resolution acquisitions, the radiofrequency coil must be optimized for the marmoset; however, relatively few custom coils have been developed that maximize SNR and are compatible with accelerated acquisitions. For the study of large populations of animals, the heterogeneity in animal size reduces the effectiveness of a "one size fits all" approach to coil sizing and makes coils tailored to individual animals cost and time prohibitive. The approach taken in this study was to create an 8-channel phased-array receive coil that was adjustable to the width of the marmoset head, thereby negating the need for tailored coils while still maintaining high SNR. Two marmosets of different size were imaged on a 9.4-T small-animal scanner. Consistent SNR was achieved in the periphery of the brain between head sizes. When compared to a 15-channel, "one size fits all" receive coil, the adjustable coil achieved 57% higher SNR in the superior frontal and parietal cortices and 29% higher SNR in the centre of the brain. The mean geometry factor of the adjustable coil was less than 1.2 for a 2-fold reduction factor in the left-right and anterior-posterior directions. Geometry factors were compared to the 15-channel coil to guide future designs. The adjustable coil was shown to be a practical means for anatomical and echo-planar imaging of marmoset cohorts.

Right ventricular function after coronary artery bypass graft surgery--a magnetic resonance imaging study.

BACKGROUND: A reduction in right ventricular function commonly occurs in the early postoperative period after coronary artery bypass graft surgery (CABG). We sought to determine the longer-term effect of CABG on right ventricular function. METHODS: Cardiac magnetic resonance imaging was performed before and approximately 3 months after surgery in 28 patients undergoing elective CABG. Right ventricular (RV) ejection fraction was assessed by planimetry of electrocardiographically gated cine images. RESULTS: There was a statistically significant increase in left ventricular ejection fraction from 50% to 58% (P=.003) after CABG. RV ejection fraction also increased from 54% to 60% (P=.002). In patients with lower baseline RV ejection fraction (below the median, < 53%), this parameter improved from 47% to 57% (P<.001). Both on-pump (47% vs. 62%, P=.003) as well as off-pump CABG (47% vs. 55%, P=.009) lead to an improvement in RV function in patients in the initial low RV ejection fraction group. CONCLUSION: Long-term right ventricular function was not adversely affected by CABG. An improvement in RV function occurred after surgery in patients with low baseline RV ejection fraction and was similar in patients who underwent surgery with or without cardiopulmonary bypass.

Cardiovascular magnetic resonance T2 signal abnormalities in left ventricular ballooning syndrome.

Left ventricular ballooning syndrome (LVBS), also known as Takotsubo cardiomyopathy, is characterized by regional left ventricular dysfunction associated with severe psychological stress. T2 weighted cardiac magnetic resonance (CMR) can identify myocardial edema due to ischemia or other insults. A standard clinical CMR scan with double inversion recovery fast spin echo T2 weighted sequences was performed on consecutive patients with LVBS. T2 signal was compared in myocardial segments with normal and impaired function based on systolic wall thickening (SWT). Eight LVBS patients were identified, all female, with a median age of 61 years and median left ventricular ejection fraction of 52%. Four patients had apical ballooning and four had mid-wall or basal ballooning. In severely dysfunctional segments (those with SWT < 25%), the median percentage of high T2 signal was 85 compared with 35 in those with SWT > 25% (P < 0.001). When the segments were categorized into tertiles based on SWT, the percentage of high T2 signal was greatest in segments with the worst function (68% vs. 43% vs. 31%, P = 0.005). In the five patients who returned for follow up, there was a significant reduction in high T2 signal compared with baseline in those segments that were initially severely dysfunctional (85% vs. 35%, P < 0.001). In conclusion, we describe elevated T2 signal consistent with myocardial edema in patients with LVBS. The T2 signal is highest in myocardium with the most impaired function and resolves over time.

Cell tracking and therapy evaluation of bone marrow monocytes and stromal cells using SPECT and CMR in a canine model of myocardial infarction.

BACKGROUND: The clinical application of stem cell therapy for myocardial infarction will require the development of methods to monitor treatment and pre-clinical assessment in a large animal model, to determine its effectiveness and the optimum cell population, route of delivery, timing, and flow milieu. OBJECTIVES: To establish a model for a) in vivo tracking to monitor cell engraftment after autologous transplantation and b) concurrent measurement of infarct evolution and remodeling. METHODS: We evaluated 22 dogs (8 sham controls, 7 treated with autologous bone marrow monocytes, and 7 with stromal cells) using both imaging of 111Indium-tropolone labeled cells and late gadolinium enhancement CMR for up to12 weeks after a 3 hour coronary occlusion. Hearts were also examined using immunohistochemistry for capillary density and presence of PKH26 labeled cells. RESULTS: In vivo Indium imaging demonstrated an effective biological clearance half-life from the injection site of ~5 days. CMR demonstrated a pattern of progressive infarct shrinkage over 12 weeks, ranging from 67-88% of baseline values with monocytes producing a significant treatment effect. Relative infarct shrinkage was similar through to 6 weeks in all groups, following which the treatment effect was manifest. There was a trend towards an increase in capillary density with cell treatment. CONCLUSION: This multi-modality approach will allow determination of the success and persistence of engraftment, and a correlation of this with infarct size shrinkage, regional function, and left ventricular remodeling. There were overall no major treatment effects with this particular model of transplantation immediately post-infarct.