Essentials for Interpreting Intracranial Vessel Wall MRI Results: State of the Art.

Intracranial vessel wall (VW) MRI has become widely available in clinical practice, providing multiple uses for evaluation of neurovascular diseases. The Vessel Wall Imaging Study Group of the American Society of Neuroradiology has recently reported expert consensus recommendations for the clinical implementation of this technique. However, the complexity of the neurovascular system and caveats to the technique may challenge its application in clinical practice. The purpose of this article is to review concepts essential for accurate interpretation of intracranial VW MRI results. This knowledge is intended to improve diagnostic confidence and performance in the interpretation of VW MRI scans. © RSNA, 2021 Online supplemental material is available for this article.

Fast whole brain MR imaging of dynamic susceptibility contrast changes in the cerebrospinal fluid (cDSC MRI).

PURPOSE: The circulation of cerebrospinal fluid (CSF) is closely associated with many aspects of brain physiology. When gadolinium(Gd)-based contrast is administered intravenously, pre- and post-contrast MR signal changes can often be observed in the CSF at certain locations within the intra-cranial space, mainly due to the lack of a blood-brain barrier in the dural blood vessels. This study aims to develop and systemically optimize MRI sequences that can detect dynamic signal changes in the CSF after Gd administration with a sub-millimeter spatial resolution, a temporal resolution of <10 s, and whole brain coverage. METHODS: Bloch simulations were performed to determine optimal imaging parameters for maximum CSF contrast before and after Gd injection. Simulations were validated with phantom scans. An optimized turbo-spin-echo (TSE) sequence was performed on healthy volunteers on 3T and 7T. RESULTS: Simulation results agreed well with phantom scans. In human scans, dynamic signal changes after Gd injection in the CSF were detected at several locations where cerebral lymphatic vessels were identified in previous studies. The concentration of Gd in CSF in these regions was estimated to be approximately 0.2 mmol/L. CONCLUSION: Dynamic signal changes induced by the distribution of Gd in the CSF can be detected in healthy human subjects with an optimized TSE sequence. The proposed methodology does not rely on any particular theory on CSF circulation. We expect it to be useful for studies on CSF circulation and cerebral lymphatic vessels in the brain.

Neural mechanisms of economic choices in mice.

Economic choices entail computing and comparing subjective values. Evidence from primates indicates that this behavior relies on the orbitofrontal cortex. Conversely, previous work in rodents provided conflicting results. Here we present a mouse model of economic choice behavior, and we show that the lateral orbital (LO) area is intimately related to the decision process. In the experiments, mice chose between different juices offered in variable amounts. Choice patterns closely resembled those measured in primates. Optogenetic inactivation of LO dramatically disrupted choices by inducing erratic changes of relative value and by increasing choice variability. Neuronal recordings revealed that different groups of cells encoded the values of individual options, the binary choice outcome and the chosen value. These groups match those previously identified in primates, except that the neuronal representation in mice is spatial (in monkeys it is good-based). Our results lay the foundations for a circuit-level analysis of economic decisions.

Multi-atlas tool for automated segmentation of brain gray matter nuclei and quantification of their magnetic susceptibility.

Quantification of tissue magnetic susceptibility using MRI offers a non-invasive measure of important tissue components in the brain, such as iron and myelin, potentially providing valuable information about normal and pathological conditions during aging. Despite many advances made in recent years on imaging techniques of quantitative susceptibility mapping (QSM), accurate and robust automated segmentation tools for QSM images that can help generate universal and sharable susceptibility measures in a biologically meaningful set of structures are still not widely available. In the present study, we developed an automated process to segment brain nuclei and quantify tissue susceptibility in these regions based on a susceptibility multi-atlas library, consisting of 10 atlases with T1-weighted images, gradient echo (GRE) magnitude images and QSM images of brains with different anatomic patterns. For each atlas in this library, 10 regions of interest in iron-rich deep gray matter structures that are better defined by QSM contrast were manually labeled, including caudate, putamen, globus pallidus internal/external, thalamus, pulvinar, subthalamic nucleus, substantia nigra, red nucleus and dentate nucleus in both left and right hemispheres. We then tested different pipelines using different combinations of contrast channels to bring the set of labels from the multi-atlases to each target brain and compared them with the gold standard manual delineation. The results showed that the segmentation accuracy using dual contrasts QSM/T1 pipeline outperformed other dual-contrast or single-contrast pipelines. The dice values of 0.77 ±â€¯0.09 using the QSM/T1 multi-atlas pipeline rivaled with the segmentation reliability obtained from multiple evaluators with dice values of 0.79 ±â€¯0.07 and gave comparable or superior performance in segmenting subcortical nuclei in comparison with standard FSL FIRST or recent multi-atlas package of volBrain. The segmentation performance of the QSM/T1 multi-atlas was further tested on QSM images acquired using different acquisition protocols and platforms and showed good reliability and reproducibility with average dice of 0.79 ±â€¯0.08 to manual labels and 0.89 ±â€¯0.04 in an inter-protocol manner. The extracted quantitative magnetic susceptibility values in the deep gray matter nuclei also correlated well between different protocols with inter-protocol correlation constants all larger than 0.97. Such reliability and performance was ultimately validated in an external dataset acquired at another study site with consistent susceptibility measures obtained using the QSM/T1 multi-atlas approach in comparison to those using manual delineation. In summary, we designed a susceptibility multi-atlas tool for automated and reliable segmentation of QSM images and for quantification of magnetic susceptibilities. It is publicly available through our cloud-based platform (www.mricloud.org). Further improvement on the performance of this multi-atlas tool is expected by increasing the number of atlases in the future.

Added value of contrast echocardiography in characterization of nonischemic cardiomyopathy.

Nonischemic cardiomyopathy (NICM) is a group of noncoronary heterogonous myocardial diseases. The heterogonous nature of NICM has impeded its diagnosis. In the present case series, we demonstrate the added value of using contrast echocardiography in the characterization of NICM. Two patients of advanced age were admitted for possible acute coronary syndrome, which was subsequently excluded by coronary angiography. Conventional and contrast echocardiography revealed characteristic structural and dynamic features of the left ventricle that were compatible with two distinct NICM diseases: stress-induced cardiomyopathy and noncompaction of the ventricular myocardium. Contrast echocardiography characterizes the cardiac structure and allows for real-time assessment of myocardial motion and perfusion. It may help to distinguish diseases with different etiologies.

Different profiles of main and accessory olfactory bulb mitral/tufted cell projections revealed in mice using an anterograde tracer and a whole-mount, flattened cortex preparation.

A whole-mount, flattened cortex preparation was developed to compare profiles of axonal projections from main olfactory bulb (MOB) and accessory olfactory bulb (AOB) mitral and tufted (M/T) cells. After injections of the anterograde tracer, Phaseolus vulgaris leucoagglutinin, mapping of labeled axons using a Neurolucida system showed that M/T cells in the AOB sent axons primarily to the medial and posterior lateral cortical amygdala, with minimal branching into the piriform cortex. By contrast, M/T cells in the MOB displayed a network of collaterals that branched off the primary axon at several levels of the lateral olfactory tract (LOT). Collaterals emerging from the LOT into the anterior piriform cortex were often observed crossing into the posterior piriform cortex. M/T cells in the dorsal MOB extended fewer collaterals from the primary axon in the rostral LOT than did M/T cells from the anterior or ventral MOB. MOB M/T cells that projected to the medial amygdala did not do so exclusively, also sending collaterals to the anterior cortical amygdala as well as to olfactory cortical regions. This arrangement may be related to the ability of social experience to modify the response of mice to volatile pheromones detected by the main olfactory system.

A direct main olfactory bulb projection to the 'vomeronasal' amygdala in female mice selectively responds to volatile pheromones from males.

The main olfactory system, like the accessory olfactory system, responds to pheromones involved in social communication. Whereas pheromones detected by the accessory system are transmitted to the hypothalamus via the medial ('vomeronasal') amygdala, the pathway by which pheromones are detected and transmitted by the main system is not well understood. We examined in female mice whether a direct projection from mitral/tufted (M/T) cells in the main olfactory bulb (MOB) to the medial amygdala exists, and whether medial amygdala-projecting M/T cells are activated by volatile urinary odors from conspecifics or a predator (cat). Simultaneous anterograde tracing using Phaseolus vulgaris leucoagglutinin and Fluoro-Ruby placed in the MOB and accessory olfactory bulb (AOB), respectively, revealed that axons of MOB M/T cells projected to superficial laminae of layer Ia in anterior and posterodorsal subdivisions of the medial amygdala, whereas projection neurons from the AOB sent axons to non-overlapping, deeper layer Ia laminae of the same subdivisions. Placement of the retrograde tracer cholera toxin B into the medial amygdala labeled M/T cells that were concentrated in the ventral MOB. Urinary volatiles from male mice, but not from female conspecifics or cat, induced Fos in medial amygdala-projecting MOB M/T cells of female subjects, suggesting that information about male odors is transmitted directly from the MOB to the 'vomeronasal' amygdala. The presence of a direct MOB-to-medial amygdala pathway in mice and other mammals could enable volatile, opposite-sex pheromones to gain privileged access to diencephalic structures that control mate recognition and reproduction.

Differential gene expression between sensory neocortical areas: potential roles for Ten_m3 and Bcl6 in patterning visual and somatosensory pathways.

Adult neocortical areas are characterized by marked differences in cytoarchitecture and connectivity that underlie their functional roles. The molecular determinants of these differences are largely unknown. We performed a microarray analysis to identify molecules that define the somatosensory and visual areas during the time when afferent and efferent projections are forming. We identified 122 molecules that are differentially expressed between the regions and confirmed by quantitative polymerase chain reaction 95% of the 20 genes tested. Two genes were chosen for further investigation: Bcl6 and Ten_m3. Bcl6 was highly expressed in the superficial cortical plate corresponding to developing layer IV of somatosensory cortex at postnatal day (P) 0. This had diminished by P3, but strong expression was found in layer V pyramidal cells by P7 and was maintained until adulthood. Retrograde tracing showed that Bcl6 is expressed in corticospinal neurons. Ten_m3 was expressed in a graded pattern within layer V of caudal cortex that corresponds well with visual cortex. Retrograde tracing and immunostaining showed that Ten_m3 is highly expressed along axonal tracts of projection neurons of the developing visual pathway. Overexpression demonstrated that Ten_m3 promotes homophilic adhesion and neurite outgrowth in vivo. This suggests an important role for Ten_m3 in the development of the visual pathway.

Effect of bilateral accessory olfactory bulb lesions on volatile urinary odor discrimination and investigation as well as mating behavior in male mice.

Previous research raises the possibility that urinary volatiles from estrous female mice activate mitral cells in the accessory olfactory bulb (AOB) of male mice following detection via the main olfactory epithelium as opposed to the vomeronasal organ. We asked whether bilateral lesions of the AOB would disrupt the ability of male mice to discriminate between urinary volatiles from mice of different sexes or endocrine states, or affect their interest in investigating these odors when they were presented sequentially in home-cage habituation/dishabituation tests. Males with either partial or complete bilateral lesions of the AOB resembled sham-operated control males in their ability to discriminate between ovariectomized and estrous female urinary volatiles as well as between male and estrous female urinary volatiles. However, males with either complete or partial AOB lesions spent significantly less time than sham-operated control males investigating urinary volatiles from estrous females, especially during tests when the alternative stimulus presented was male urine. Placement of AOB lesions failed to disrupt males' mating performance. Our results suggest that the incentive value of opposite-sex (female) volatile urinary odors which are initially detected by the main olfactory system is enhanced when they are further processed by the male's AOB.

Development of sex differences in the principal nucleus of the bed nucleus of the stria terminalis of mice: role of Bax-dependent cell death.

Neuron number in the principal nucleus of the bed nucleus of the stria terminalis (BNSTp) is greater in adult male mice than in females. Deletion of the proapoptotic gene, Bax, increases the number of BNSTp cells in adulthood and eliminates the sex difference in cell number. Here, we map the ontogeny of sex differences in nuclear volume and cell number in the BNSTp of neonatal mice, and evaluate the role of cell death in the development of these differences. We find that BNSTp volume and cell number do not differ between male and female wild-type mice on postnatal days P3, P5, or P7. Sex differences emerge after the first postnatal week and both measures are significantly greater in males than in females on P9 and P11. Cell death, assessed by TUNEL staining, was observed in the BNSTp of both sexes from P1-P8. Females had more TUNEL-positive cells than males from approximately P3-P6, with the maximum number of dying cells observed on P5/P6. To test whether the Bax gene is required for sexually dimorphic cell death in the BNSTp, TUNEL cells were counted on P6 in Bax -/- mice and their Bax +/+ siblings. Bax gene deletion nearly abolished TUNEL-positive cells in the BNSTp of both sexes. Together, these findings support the interpretation that the sex difference in BNSTp cell number seen in adulthood is due to Bax-dependent, sexually dimorphic cell death during the first week of life.

Sex difference in Fos induced by male urine in medial amygdala-projecting accessory olfactory bulb mitral cells of mice.

We previously reported that exposure to soiled male bedding induced Fos protein immunoreactivity (Fos-IR) in significantly more neurons of the vomeronasal organ (VNO) and medial amygdala of gonadectomized, estradiol-treated female than male mice whereas no such sex difference was seen in the intervening mitral cells of the accessory olfactory bulb (AOB). We asked whether a sexually dimorphic functional response to male urinary pheromones might be revealed in AOB mitral cells that project specifically to the medial amygdala. Gonadectomized mice of both sexes were treated with estradiol and 3 days later received bilateral injections of the retrograde tracer, Cholera toxin-B (CTB) into the medial amygdala. Five days later male urine or saline was applied nasally to each subject 90 min prior to sacrifice, and sections of the AOB were processed for double-label fluorescent immunocytochemistry for Fos protein and CTB. In both the rostral and caudal AOB, there were significantly more double-labeled mitral cells in female than in male subjects following exposure to male urine. A sex difference in the responsiveness of VNO sensory neurons seen previously to male soiled bedding is reflected in a parallel sex difference in the responsiveness of AOB mitral cells when only AOB cells that project to the amygdala are examined and when male urine as opposed to soiled male bedding is used as the activating stimulus.