Mobile point-of-care MRI demonstration of a normal volunteer in a telemedicine-equipped ambulance.

OBJECTIVE: Several centers have implemented ambulances equipped with CT scanners and telemedicine capabilities, known as mobile stroke units (MSU), to expedite acute stroke care delivery in the pre-hospital setting. While MSUs have been shown to improve outcomes compared with standard emergency medical management, there are limitations to incorporating CT, including radiation exposure to emergency medical services personnel. Recently, a portable, low-field strength MRI (Swoop®, Hyperfine, Inc., Guilford, CT) received FDA clearance for in-hospital use. Here, as proof-of-concept, we explore the possibility of performing MRI in a telemedicine-equipped ambulance during active transport. MATERIALS AND METHODS: In this initial technical demonstration, we imaged an MR phantom and a normal human volunteer using a standard stroke protocol during active ambulance transport. RESULTS: Images of the MR phantom and volunteer were successfully obtained and were immediately available for viewing in the hospital PACS system. The images were deemed of diagnostic quality by the radiologist. Active motion correction maintained superior image quality despite vehicle and scanner motion. In-plane, low contrast resolution of greater than 4 × 4 mm was achieved. Average transmit speeds were calculated to be 3.54 Megabits/second and upload data rates varied while in transit ranging from 8.54 to 4.13 Megabits/second. CONCLUSION: While MRI is not yet ready for clinical use in the MSU setting, our initial experience suggests potential technological feasible of this approach following future technical and MRI sequence development. Additional studies, incorporating patients, would be required to determine clinical feasibility.

Epilepsy-related cytoarchitectonic abnormalities along white matter pathways.

OBJECTIVE: Temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy. Unfortunately, the clinical outcomes of TLE cannot be determined based only on current diagnostic modalities. A better understanding of white matter (WM) connectivity changes in TLE may aid the identification of network abnormalities associated with TLE and the phenotypic characterisation of the disease. METHODS: We implemented a novel approach for characterising microstructural changes along WM pathways using diffusional kurtosis imaging (DKI). Along-the-tract measures were compared for 32 subjects with left TLE and 36 age-matched and gender-matched controls along the left and right fimbria-fornix (FF), parahippocampal WM bundle (PWMB), arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF) and cingulum bundle (CB). Limbic pathways were investigated in relation to seizure burden and control with antiepileptic drugs. RESULTS: By evaluating measures along each tract, it was possible to identify abnormalities localised to specific tract subregions. Compared with healthy controls, subjects with TLE demonstrated pathological changes in circumscribed regions of the FF, PWMB, UF, AF and ILF. Several of these abnormalities were detected only by kurtosis-based and not by diffusivity-based measures. Structural WM changes correlated with seizure burden in the bilateral PWMB and cingulum. CONCLUSIONS: DKI improves the characterisation of network abnormalities associated with TLE by revealing connectivity abnormalities that are not disclosed by other modalities. Since TLE is a neuronal network disorder, DKI may be well suited to fully assess structural network abnormalities related to epilepsy and thus serve as a tool for phenotypic characterisation of epilepsy.

Thyroid Doses and Risks to Adult Patients Undergoing Neck CT Examinations.

OBJECTIVE: The purpose of this study was to estimate absorbed thyroid dose and consequent cancer risks in adult patients undergoing neck CT examinations. MATERIALS AND METHODS: We used data from neck CT examinations of 68 consecutive adult patients to calculate the thyroid dose and estimate the corresponding cancer risk. Age and sex were recorded along with the volume CT dose index (CTDIvol) that was used to perform the examination. CTDIvol values were used to estimate thyroid doses in the mathematic phantom used in the ImPACT patient CT dosimetry calculator. Corresponding doses in patients were estimated by modeling each patient's neck as an equivalent cylinder of water and applying correction factors for varying neck size and scanning length and the variation of radiation intensity due to automatic exposure control. RESULTS: The mean (± SD) adult patient age was 59 ± 16 years, and the mean equivalent water cylinder diameter used for modeling the patient neck was 19.4 ± 4.2 cm. The average adult patient neck size was about 3 cm larger than the mathematic anthropomorphic phantom (16.5 cm), decreasing the estimated thyroid doses by 15%. Thyroid doses were independent of age and sex, with an average of 50 ± 23 mGy. The average cancer risk for a 20-year-old woman was six times higher than the corresponding risk for a 20-year-old man. Increasing patient age of either sex from 40 to 60 years reduced the cancer risk by approximately an order of magnitude. CONCLUSION: Patient sex and age are the most important factors in determining thyroid cancer risk, with the thyroid dose being secondary.

Stroke assessment with diffusional kurtosis imaging.

BACKGROUND AND PURPOSE: Despite being the gold standard technique for stroke assessment, conventional diffusion MRI provides only partial information about tissue microstructure. Diffusional kurtosis imaging is an advanced diffusion MRI method that yields, in addition to conventional diffusion information, the diffusional kurtosis, which may help improve characterization of tissue microstructure. In particular, this additional information permits the description of white matter (WM) in terms of WM-specific diffusion metrics. The goal of this study is to elucidate possible biophysical mechanisms underlying ischemia using these new WM metrics. METHODS: We performed a retrospective review of clinical and diffusional kurtosis imaging data of 44 patients with acute/subacute ischemic stroke. Patients with a history of brain neoplasm or intracranial hemorrhages were excluded from this study. Region of interest analysis was performed to measure percent change of diffusion metrics in ischemic WM lesions compared with the contralateral hemisphere. RESULTS: Kurtosis maps exhibit distinct ischemic lesion heterogeneity that is not apparent on apparent diffusion coefficient maps. Kurtosis metrics also have significantly higher absolute percent change than complementary conventional diffusion metrics. Our WM metrics reveal an increase in axonal density and a larger decrease in the intra-axonal (Da) compared with extra-axonal diffusion microenvironment of the ischemic WM lesion. CONCLUSIONS: The well-known decrease in the apparent diffusion coefficient of WM after ischemia is found to be mainly driven by a significant drop in the intra-axonal diffusion microenvironment. Our results suggest that ischemia preferentially alters intra-axonal environment, consistent with a proposed mechanism of focal enlargement of axons known as axonal swelling or beading.

Medial temporal lobe epilepsy is associated with neuronal fibre loss and paradoxical increase in structural connectivity of limbic structures.

BACKGROUND: It has been hypothesised that seizure induced neuronal loss and axonal damage in medial temporal lobe epilepsy (MTLE) may lead to the development of aberrant connections between limbic structures and eventually result in the reorganisation of the limbic network. In this study, limbic structural connectivity in patients with MTLE was investigated, using diffusion tensor MRI, probabilistic tractography and graph theory based network analysis. METHODS: 12 patients with unilateral MTLE and hippocampal sclerosis (five left and seven right MTLE) and 26 healthy controls were studied. The connectivity of 10 bilateral limbic regions of interest was mapped with probabilistic tractography, and the probabilistic fibre density between each pair of regions was used as the measure of their weighted structural connectivity. Binary connectivity matrices were then obtained from the weighted connectivity matrix using a range of fixed density thresholds. Graph theory based properties of nodes (degree, local efficiency, clustering coefficient and betweenness centrality) and the network (global efficiency and average clustering coefficient) were calculated from the weight and binary connectivity matrices of each subject and compared between patients and controls. RESULTS: MTLE was associated with a regional reduction in fibre density compared with controls. Paradoxically, patients exhibited (1) increased limbic network clustering and (2) increased nodal efficiency, degree and clustering coefficient in the ipsilateral insula, superior temporal region and thalamus. There was also a significant reduction in clustering coefficient and efficiency of the ipsilateral hippocampus, accompanied by increased nodal degree. CONCLUSIONS: These results suggest that MTLE is associated with reorganisation of the limbic system. These results corroborate the concept of MTLE as a network disease, and may contribute to the understanding of network excitability dynamics in epilepsy and MTLE.

Technical note: estimating absorbed doses to the thyroid in CT.

PURPOSE: To describe a method for estimating absorbed doses to the thyroid in patients undergoing neck CT examinations. METHODS: Thyroid doses in anthropomorphic phantoms were obtained for all 23 scanner dosimetry data sets in the ImPACT CT patient dosimetry calculator. Values of relative thyroid dose [R(thy)(L)], defined as the thyroid dose for a given scan length (L) divided by the corresponding thyroid dose for a whole body scan, were determined for neck CT scans. Ratios of the maximum thyroid dose to the corresponding CTDI(vol) and [D'(thy)], were obtained for two phantom diameters. The mass-equivalent water cylinder of any patient can be derived from the neck cross-sectional area and the corresponding average Hounsfield Unit, and compared to the 16.5-cm diameter water cylinder that models the ImPACT anthropomorphic phantom neck. Published values of relative doses in water cylinders of varying diameter were used to adjust thyroid doses in the anthropomorphic phantom to those of any sized patient. RESULTS: Relative thyroid doses R(thy)(L) increase to unity with increasing scan length and with very small difference between scanners. A 10-cm scan centered on the thyroid would result in a dose that is, nearly 90% of the thyroid dose from a whole body scan when performed using the constant radiographic techniques. At 120 kV, the average value of D'(thy) for the 16-cm diameter was 1.17 +/- 0.05 and was independent of CT vendor and year of CT scanner, and choice of x-ray tube voltage. The corresponding average value of D'(thy) in the 32-cm diameter phantom was 2.28 +/- 0.22 and showed marked variations depending on vendor, year of introduction into clinical practice as well as x-ray tube voltage. At 120 kV, a neck equivalent to a 10-cm diameter cylinder of water would have thyroid doses 36% higher than those in the ImPACT phantom, whereas a neck equivalent to a 25-cm cylinder diameter would have thyroid doses 35% lower. CONCLUSIONS: Patient thyroid doses can be estimated by taking into account the amount of radiation used to perform the CT examination (CTDI(vol)) and accounting for scan length and patient anatomy (i.e., neck diameter) at the thyroid location.

Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OCSCC) is a prevalent surgically treated subset of head and neck cancer with frequent recurrence and poor survival. Immunotherapy has demonstrated efficacy in recurrent/metastatic head and neck cancer. However, whether antitumor responses could be fostered by neoadjuvant presurgical immunotherapy remains unclear. Using a Simon's two-stage design, we present results of a single-arm phase-II trial where 12 patients with stage II-IVA OCSCC received 3 to 4 biweekly doses of 3 mg/kg nivolumab followed by definitive surgical resection with curative intent. Presurgical nivolumab therapy in this cohort shows an overall response rate of 33% (n = 4 patients; 95% CI: 12%-53%). With a median follow up of 2.23 years, 10 out of 12 treated patients remain alive. Neoadjuvant nivolumab is safe, well-tolerated, and is not associated with delays in definitive surgical treatment in this study. This work demonstrates feasibility and safety for incorporation of nivolumab in the neoadjuvant setting for OCSCC (ClinicalTrials.gov: NCT03021993).

Early assessment of recurrent glioblastoma response to bevacizumab treatment by diffusional kurtosis imaging: a preliminary report.

PURPOSE: The purpose of this preliminary study is to apply diffusional kurtosis imaging to assess the early response of recurrent glioblastoma to bevacizumab treatment. METHODS: This prospective cohort study included 10 patients who had been diagnosed with recurrent glioblastoma and scheduled to receive bevacizumab treatment. Diffusional kurtosis images were obtained from all the patients 0-7 days before (pre-bevacizumab) and 28 days after (post-bevacizumab) initiating bevacizumab treatment. The mean, 10th, and 90th percentile values were derived from the histogram of diffusional kurtosis imaging metrics in enhancing and non-enhancing lesions, selected on post-contrast T1-weighted and fluid-attenuated inversion recovery images. Correlations of imaging measures with progression-free survival and overall survival were evaluated using Spearman's rank correlation coefficient. The significance level was set at P < 0.05. RESULTS: Higher pre-bevacizumab non-enhancing lesion volume was correlated with poor overall survival (r = -0.65, P = 0.049). Higher post-bevacizumab mean diffusivity and axial diffusivity (D∥, D∥10% and D∥90%) in non-enhancing lesions were correlated with poor progression-free survival (r = -0.73, -0.83, -0.71 and -0.85; P < 0.05). Lower post-bevacizumab axial kurtosis (K∥10%) in non-enhancing lesions was correlated with poor progression-free survival (r = 0.81, P = 0.008). CONCLUSIONS: This preliminary study demonstrates that diffusional kurtosis imaging metrics allow the detection of tissue changes 28 days after initiating bevacizumab treatment and that they may provide information about tumor progression.

Perilesional apparent diffusion coefficient in the preoperative evaluation of glioma grade.

Preoperative identification of high-grade gliomas is critical to optimize treatment strategy and to predict prognosis. To determine whether perilesional apparent diffusion coefficient (ADC) values differ between high- and low-grade tumors, we assessed water diffusivity within normal-appearing brain parenchyma (NABP) surrounding gliomas in twenty-one treatment-naïve patients. This showed significantly lower mean and 25th percentile (Q1) ADC values in high- grade compared to low-grade gliomas respectively in the range of 10-25 and 10-30 mm away from combined tumor and surrounding T2 signal. Thus, perilesional ADC measurement may reflect the extent of tumor infiltration beyond the abnormality seen on conventional MRI.

Individual variability in the anatomical distribution of nodes participating in rich club structural networks.

With recent advances in computational analyses of structural neuroimaging, it is possible to comprehensively map neural connectivity, i.e., the brain connectome. The architectural organization of the connectome is believed to play an important role in several biological processes. Central to the conformation of the connectome are connectivity hubs, which are likely to be organized in accordance with the rich club phenomenon, as evidenced by graph theory analyses of neural architecture. It is yet unclear whether rich club connectivity hubs are consistently organized in the same anatomical framework across healthy adults. We constructed the brain connectome from 43 healthy adults, based on T1-weighted and diffusion tensor MRI data. Probabilistic fiber tractography was used to evaluate connectivity between each possible pair of cortical anatomical regions of interest. Connectivity hubs were identified in accordance with the rich club phenomenon applied to binarized matrices, and the variability in frequency of hub participation was assessed node-wise across all subjects. The anatomical location of nodes participating in rich club networks was fairly consistent across subjects. The most common locations for rich club nodes were identified in integrative areas, such as the cingulate and pericingulate regions, medial aspect of the occipital areas and precuneus; or else, they were found in important and specialized brain regions (such as the oribitofrontal cortex, caudate, fusiform gyrus, and hippocampus). Marked anatomical consistency exists across healthy brains in terms of nodal participation and location of rich club networks. The consistency of connections between integrative areas and specialized brain regions highlights a fundamental connectivity pattern shared among healthy brains. We propose that approaching brain connectivity with this framework of anatomical consistencies may have clinical implications for early detection of individual variability.

Human brain asymmetry in microstructural connectivity demonstrated by diffusional kurtosis imaging.

Structural asymmetry of whole brain white matter (WM) pathways, i.e., the connectome, has been demonstrated using fiber tractography based on diffusion tensor imaging (DTI). However, DTI-based tractography fails to resolve axonal fiber bundles that intersect within an imaging voxel, and therefore may not fully characterize the extent of asymmetry. The goal of this study was to assess structural asymmetry with tractography based on diffusional kurtosis imaging (DKI), which improves upon DTI-based tractography by delineating intravoxel crossing fibers. DKI images were obtained from 42 healthy subjects. By using automatic segmentation, gray matter (GM) was parcellated into anatomically defined regions of interest (ROIs). WM pathways were reconstructed with both DKI- and DTI-based tractography. The connectivity between the ROIs was quantified with the streamlines connecting the ROIs. The asymmetry index (AI) was utilized to quantify hemispheric differences in the connectivity of cortical ROIs and of links interconnecting cortical ROIs. Our results demonstrated that leftward asymmetrical ROIs and links were observed in frontal, parietal, temporal lobes, and insula. Rightward asymmetrical ROI and links were observed in superior frontal lobe, cingulate cortex, fusiform, putamen, and medial temporal lobe. Interestingly, these observed structural asymmetries were incompletely identified with DTI-based tractography. These results suggest that DKI-based tractography can improve the identification of asymmetrical connectivity patterns, thereby serving as an additional tool in the evaluation of the structural bases of functional lateralization.

Computation of thyroid doses and carcinogenic radiation risks to patients undergoing neck CT examinations.

The aim of the study was to investigate how differences in patient anatomy and CT technical factors in neck CT impact on thyroid doses and the corresponding carcinogenic risks. The CTDIvol and dose-length product used in 11 consecutive neck CT studies, as well as data on automatic exposure control (AEC) tube current variation(s) from the image DICOM header, were recorded. For each CT image that included the thyroid, the mass equivalent water cylinder was estimated based on the patient cross-sectional area and average relative attenuation coefficient (Hounsfield unit, HU). Patient thyroid doses were estimated by accounting for radiation intensity at the location of the patient's thyroid, patient size and the scan length. Thyroid doses were used to estimate thyroid cancer risks as a function of patient demographics using risk factors in BEIR VII. The length of the thyroid glands ranged from 21 to 54 mm with an average length of 42 ± 12 mm. Water cylinder diameters corresponding to the central slice through the patient thyroid ranged from 18 to 32 cm with a mean of 25 ± 5 cm. The average CTDIvol (32-cm phantom) used to perform these scans was 26 ± 6 mGy, but the use of an AEC increased the tube current by an average of 44 % at the thyroid mid-point. Thyroid doses ranged from 29 to 80 mGy, with an average of 55 ± 19 mGy. A 20-y-old female receiving the highest thyroid dose of 80 mGy would have a thyroid cancer risk of nearly 0.1 %, but radiation risks decreased very rapidly with increasing patient age. The key factors that affect thyroid doses in neck CT examinations are the radiation intensity at the thyroid location and the size of the patient. The corresponding patient thyroid cancer risk is markedly influenced by patient sex and age.

White matter hyperintensities predict low frequency hearing in older adults.

Vascular disease has been proposed as a contributing factor for presbyacusis (age-related hearing loss). While this hypothesis is supported by pathological evidence of vascular decline in post-mortem human and animal studies, evidence in human subjects has been mixed with associations typically reported between a measure of vascular health and low frequency hearing in older women. Given the difficulty of characterizing the in vivo health of the cochlear artery in humans, an estimate of cerebral small vessel disease was used to test the prediction that age-related change in low frequency hearing and not high frequency hearing is related to a global decline in vascular health. We examined the extent to which these associations were specific to women and influenced by a history of high blood pressure in 72 older adults (mean age 67.12 years, SD = 8.79). Probability estimates of periventricular white matter hyperintensities (WMH) from T1- and fluid attenuated T2-weighted magnetic resonance images were significantly associated with a low frequency hearing metric across the sample, which were independent of age, but driven by women and people with a history of high blood pressure. These results support the premise that vascular declines are one mechanism underlying age-related changes in low frequency hearing.

Politics on the brain: an FMRI investigation.

We assessed political attitudes using the Implicit Association Test (IAT) in which participants were presented faces and names of well-known Democrat and Republican politicians along with positive and negative words while undergoing functional MRI. We found a significant behavioral IAT effect for the face, but not the name, condition. The fMRI face condition results indicated that ventromedial and anterior prefrontal cortices were activated during political attitude inducement. Amygdala and fusiform gyrus were activated during perceptual processing of familiar faces. Amygdala activation also was associated with measures of strength of emotion. Frontopolar activation was positively correlated with an implicit measure of bias and valence strength (how strongly the participants felt about the politicians), while strength of affiliation with political party was negatively correlated with lateral PFC, lending support to the idea that two distinct but interacting networks-one emphasizing rapid, stereotypic, and emotional associative knowledge and the other emphasizing more deliberative and factual knowledge-cooperate in the processing of politicians. Our findings of ventromedial PFC activation suggests that when processing the associative knowledge concerned with politicians, stereotypic knowledge is activated, but in addition, the anterior prefrontal activations indicate that more elaborative, reflective knowledge about the politician is activated.