Correlating hippocampal and amygdala volumes with neuropathological burden in neurodegenerative diseases using 7T postmortem MRI.

Numerous research groups worldwide have focused on postmortem imaging to bridge the resolution gap between clinical neuroimaging and neuropathology data. We developed a standardized protocol for brain embedding, imaging, and processing, facilitating alignment between antemortem MRI, postmortem MRI, and pathology to observe brain atrophy and structural damage progression over time. Using 7T postmortem ex vivo MRI, we explore the potential correlation of amygdala and hippocampal atrophy with neuropathological burden in both Down syndrome (DS) and Alzheimer's disease (AD) cohorts. Using 7T postmortem ex vivo MRI scans from 66 cases (12 DS and 54 AD) alongside a subset of antemortem scans (n=17), we correlated manually segmented hippocampal and amygdala volumes, adjusted for age, sex, and ApoE4 status, with pathological indicators such as Thal phase, Braak stage, limbic-predominant age-related TDP-43 encephalopathy (LATE) stage, hippocampal sclerosis (HS), and Lewy body (LB) stage. A significant correlation was observed between postmortem and antemortem volumes for the hippocampus, but a similar trend observed for the amygdala did not reach statistical significance. DS individuals exhibited notably smaller hippocampal and amygdala volumes compared to AD subjects. In DS, lower hippocampal and amygdala volumes correlated with more severe Braak stage, without significant associations with Thal phase. LATE and HS pathologies were uncommon in DS cases but trended toward smaller hippocampal volumes. In AD, lower hippocampal volume associated with dementia duration, advanced Thal phase, Braak stage, LATE stage, and HS presence, whereas reduced amygdala volume correlated mainly with severe LATE stage and HS, but not with Thal or Braak stages. No significant LB correlation was detected in either DS or AD cohorts. Hippocampal volume in AD appears influenced by both AD and LATE pathologies, while amygdala volume seems primarily influenced by LATE. In DS, smaller hippocampal volume, relative to AD, appears primarily influenced by tau pathology.

Hippocampal subfields and thalamic nuclei associations with clinical outcomes in multiple sclerosis: An ultrahigh field MRI study.

BACKGROUND: Previous studies have shown that thalamic and hippocampal neurodegeneration is associated with clinical decline in Multiple Sclerosis (MS). However, contributions of the specific thalamic nuclei and hippocampal subfields require further examination. OBJECTIVE: Using 7 Tesla (7T) magnetic resonance imaging (MRI), we investigated the cross-sectional associations between functionally grouped thalamic nuclei and hippocampal subfields volumes and T1 relaxation times (T1-RT) and subsequent clinical outcomes in MS. METHODS: High-resolution T1-weighted and T2-weighted images were acquired at 7T (n=31), preprocessed, and segmented using the Thalamus Optimized Multi Atlas Segmentation (THOMAS, for thalamic nuclei) and the Automatic Segmentation of Hippocampal Subfields (ASHS, for hippocampal subfields) packages. We calculated Pearson correlations between hippocampal subfields and thalamic nuclei volumes and T1-RT and subsequent multi-modal rater-determined and patient-reported clinical outcomes (∼2.5 years after imaging acquisition), correcting for confounders and multiple tests. RESULTS: Smaller volume bilaterally in the anterior thalamus region correlated with worse performance in gait function, as measured by the Patient Determined Disease Steps (PDDS). Additionally, larger volume in most functional groups of thalamic nuclei correlated with better visual information processing and cognitive function, as measured by the Symbol Digit Modalities Test (SDMT). In bilateral medial and left posterior thalamic regions, there was an inverse association between volumes and T1-RT, potentially indicating higher tissue degeneration in these regions. We also observed marginal associations between the right hippocampal subfields (both volumes and T1-RT) and subsequent clinical outcomes, though they did not survive correction for multiple testing. CONCLUSION: Ultrahigh field MRI identified markers of structural damage in the thalamic nuclei associated with subsequently worse clinical outcomes in individuals with MS. Longitudinal studies will enable better understanding of the role of microstructural integrity in these brain regions in influencing MS outcomes.

Analysis of hippocampal subfields in sickle cell disease using ultrahigh field MRI.

Sickle cell disease (SCD) is an inherited hemoglobinopathy that causes organ dysfunction, including cerebral vasculopathy and neurological complications. Hippocampal segmentation with newer and advanced 7 Tesla (7T) MRI protocols has revealed atrophy in specific subregions in other neurodegenerative and neuroinflammatory diseases, however, there is limited evidence of hippocampal involvement in SCD. Thus, we explored whether SCD may be also associated with abnormalities in hippocampal subregions. We conducted 7T MRI imaging in individuals with SCD, including the HbSS, HbSC and HbS/beta thalassemia genotypes (n = 53), and healthy race and age-matched controls (n = 47), using a customized head coil. Both T1- and T2-weighted images were used for automatic segmentation of the hippocampal subfields. Individuals with SCD had, on average, significantly smaller volume of the region including the Dentate Gyrus and Cornu Ammonis (CA) 2 and 3 as compared to the control group. Other hippocampal subregions also showed a trend towards smaller volumes in the SCD group. These findings support and extend previous reports of reduced volume in the temporal lobe in SCD patients. Further studies are necessary to investigate the mechanisms that lead to structural changes in the hippocampus subfields and their relationship with cognitive performance in SCD patients.

Non-invasive Assessment of Liver Fat in ob/ob Mice Using Ultrasound-Induced Thermal Strain Imaging and Its Correlation with Hepatic Triglyceride Content.

Non-alcoholic fatty liver disease is the accumulation of triglycerides in liver. In its malignant form, it can proceed to steatohepatitis, fibrosis, cirrhosis, cancer and ultimately liver impairment, leading to liver transplantation. In a previous study, ultrasound-induced thermal strain imaging (US-TSI) was used to distinguish between excised fatty livers from obese mice and non-fatty livers from control mice. In this study, US-TSI was used to quantify lipid composition of fatty livers in ob/ob mice (n = 28) at various steatosis stages. A strong correlation coefficient was observed (R2 = 0.85) between lipid composition measured with US-TSI and hepatic triglyceride content. Hepatic triglyceride content is used to quantify adipose tissue in liver. The ob/ob mice were divided into three groups based on the degree of steatosis that is used in clinics: none, mild and moderate. A non-parametric Kruskal-Wallis test was conducted to determine if US-TSI can potentially differentiate among the steatosis grades in non-alcoholic fatty liver disease.

A comprehensive electromagnetic evaluation of an MRI anthropomorphic head phantom.

Electromagnetic simulations are an important tool for the safety assessment of RF coils. They are a useful resource for MRI RF coil designers, especially when complemented with experimental measurements and testing using physical phantoms. Regular-shaped (spherical/cylindrical) homogeneous phantoms are the MRI standard for RF testing but are somewhat inaccurate when compared with anthropomorphic anatomies, especially at high frequencies. In this work, using a recently developed anthropomorphic heterogeneous human head phantom, studies were performed to analyze the scattering parameters (S-parameters) and the electric and magnetic field distributions using (1) the B1+ field mapping method on a 7 T human MRI scanner and (2) numerical full-wave electromagnetic simulations. All studies used the following: a recently developed six-compartment refillable 3D-printed anthropomorphic head phantom (developed from MRI scans obtained in vivo), where the phantom itself is filled in its entirety with either heterogeneous loading, or homogeneous brain or water loading, in vivo imaging, and a commercial homogeneous spherical water phantom. Our results determined that the calculated S-parameters for all the anthropomorphic head phantom models were comparable to the model that is based on the volunteer (within 17% difference of the reflection coefficient value) but differed for the commercial homogeneous spherical water phantom (within 45% difference). The experimentally measured B1+ field maps of the anthropomorphic heterogeneous and homogeneous brain head phantoms were most comparable to the in vivo measured values. The numerical simulations also show that both the anthropomorphic homogeneous water and brain phantom models were less accurate in terms of electric field intensities/distributions when compared with the segmented in-vivo-based head model and the anthropomorphic heterogeneous head phantom model. The presented data highlights the differences between the physical phantoms/phantom models, and the in vivo measurements/segmented in-vivo-based head model. The results demonstrate the usefulness of 3D-printed anthropomorphic phantoms for RF coil evaluation and testing.

Neuroimaging of Small Vessel Disease in Late-Life Depression.

Cerebral small vessel disease is associated with late-life depression, cognitive impairment, executive dysfunction, distress, and loss of life for older adults. Late-life depression is becoming a substantial public health burden, and a considerable number of older adults presenting to primary care have significant clinical depression. Even though white matter hyperintensities are linked with small vessel disease, white matter hyperintensities are nonspecific to small vessel disease and can co-occur with other brain diseases. Advanced neuroimaging techniques at the ultrahigh field magnetic resonance imaging are enabling improved characterization, identification of cerebral small vessel disease and are elucidating some of the mechanisms that associate small vessel disease with late-life depression.

Application of a recursive partitioning decision tree algorithm for the prediction of massive transfusion in civilian trauma: the MTPitt prediction tool.

BACKGROUND: A supervised machine learning algorithm was used to generate decision trees for the prediction of massive transfusion at a Level 1 trauma center. METHODS: Trauma patients who received at least one unit of RBCs and/or low-titer group O whole blood between January 1, 2015, and December 31, 2017, were included. Massive transfusion was defined as the transfusion of 10 or more units of RBCs and/or low-titer group O whole blood in the first 24 hours of admission. A recursive partitioning algorithm was used to generate two decision trees for prediction of massive transfusion using a training data set (n = 550): the first, MTPitt, was based on demographic and clinical parameters, and the second, MTPitt+Labs, also included laboratory data. Decision tree performance was compared with the Assessment of Blood Consumption score and the Trauma Associated Severe Hemorrhage score. RESULTS: The incidence of massive transfusion in the validation data set (n = 199) was 7.5%. The MTPitt decision tree had a higher balanced accuracy (81.4%) and sensitivity (86.7%) compared to an Assessment of Blood Consumption Score of 2 or higher (77.9% and 66.7%, respectively) and a Trauma Associated Severe Hemorrhage score of 9 or higher (75.0% and 73.3%, respectively), although the 95% confidence intervals overlapped. Addition of laboratory data to the MTPitt decision tree (MTPitt+Labs) resulted in a higher specificity and balanced accuracy compared to MTPitt without an increase in sensitivity. CONCLUSIONS: The MTPitt decisions trees are highly sensitive tools for identifying patients who received a massive transfusion and do not require computational resources to be implemented in the trauma setting.

In-vivo and numerical analysis of the eigenmodes produced by a multi-level Tic-Tac-Toe head transmit array for 7 Tesla MRI.

Radio-frequency (RF) field inhomogeneities and higher levels of specific absorption rate (SAR) still present great challenges in ultrahigh-field (UHF) MRI. In this study, an in-depth analysis of the eigenmodes of a 20-channel transmit Tic-Tac-Toe (TTT) RF array for 7T neuro MRI is presented. The eigenmodes were calculated for five different Z levels (along the static magnetic field direction) of the coil. Four eigenmodes were obtained for each Z level (composed of 4 excitation ports), and they were named based on the characteristics of their field distributions: quadrature, opposite-phase, anti-quadrature, and zero-phase. Corresponding finite-difference time-domain (FDTD) simulations were performed and experimental B1+ field maps were acquired using a homogeneous spherical phantom and human head (in-vivo). The quadrature mode is the most efficient and it excites the central brain regions; the opposite-phase mode excites the brain peripheral regions; anti-quadrature mode excites the head periphery; and the zero-phase mode excites cerebellum and temporal lobes. Using this RF array, up to five eigenmodes (from five different Z levels) can be simultaneously excited. The superposition of these modes has the potential to produce homogeneous excitation with full brain coverage and low levels of SAR at 7T MRI.

Correction: Design and fabrication of a realistic anthropomorphic heterogeneous head phantom for MR purposes.

[This corrects the article DOI: 10.1371/journal.pone.0183168.].

A new RF transmit coil for foot and ankle imaging at 7T MRI.

A four-channel Tic-Tac-Toe (TTT) transmit RF coil was designed and constructed for foot and ankle imaging at 7T MRI. Numerical simulations using an in-house developed FDTD package and experimental analyses using a homogenous phantom show an excellent agreement in terms of B1+ field distribution and s-parameters. Simulations performed on an anatomically detailed human lower leg model demonstrated an B1+ field distribution with a coefficient of variation (CV) of 23.9%/15.6%/28.8% and average B1+ of 0.33µT/0.56µT/0.43µT for 1W input power (i.e., 0.25W per channel) in the ankle/calcaneus/mid foot respectively. In-vivo B1+ mapping shows an average B1+ of 0.29µT over the entire foot/ankle. This newly developed RF coil also presents acceptable levels of average SAR (0.07W/kg for 10g per 1W of input power) and peak SAR (0.34W/kg for 10g per 1W of input power) over the whole lower leg. Preliminary in-vivo images in the foot/ankle were acquired using the T2-DESS MRI sequence without the use of a dedicated receive-only array.

Design and fabrication of a realistic anthropomorphic heterogeneous head phantom for MR purposes.

OBJECTIVE: The purpose of this study is to design an anthropomorphic heterogeneous head phantom that can be used for MRI and other electromagnetic applications. MATERIALS AND METHODS: An eight compartment, physical anthropomorphic head phantom was developed from a 3T MRI dataset of a healthy male. The designed phantom was successfully built and preliminarily evaluated through an application that involves electromagnetic-tissue interactions: MRI (due to it being an available resource). The developed phantom was filled with media possessing electromagnetic constitutive parameters that correspond to biological tissues at ~297 MHz. A preliminary comparison between an in-vivo human volunteer (based on whom the anthropomorphic head phantom was created) and various phantoms types, one being the anthropomorphic heterogeneous head phantom, were performed using a 7 Tesla human MRI scanner. RESULTS: Echo planar imaging was performed and minimal ghosting and fluctuations were observed using the proposed anthropomorphic phantom. The magnetic field distributions (during MRI experiments at 7 Tesla) and the scattering parameter (measured using a network analyzer) were most comparable between the anthropomorphic heterogeneous head phantom and an in-vivo human volunteer. CONCLUSION: The developed anthropomorphic heterogeneous head phantom can be used as a resource to various researchers in applications that involve electromagnetic-biological tissue interactions such as MRI.