Individual cognitive therapy reduces frontal-thalamic resting-state functional connectivity in social anxiety disorder.

Introduction: Previous neuroimaging studies in social anxiety disorders (SAD) have reported potential neural predictors of cognitive behavioral therapy (CBT)-related brain changes. However, several meta-analyses have demonstrated that cognitive therapy (CT) was superior to traditional exposure-based CBT for SAD. Objective: To explore resting-state functional connectivity (rsFC) to evaluate the response to individual CT for SAD patients. Methods: Twenty SAD patients who attended 16-week individual CT were scanned pre- and post-therapy along with twenty healthy controls (HCs). The severity of social anxiety was assessed with the Liebowitz Social Anxiety Scale (LSAS). Multi-voxel pattern analysis (MVPA) was performed on the pre-CT data to extract regions associated with a change in LSAS (∆LSAS). Group comparisons of the seed-based rsFC analysis were performed between the HCs and pre-CT patients and between the pre-and post-CT patients. Results: MVPA-based regression analysis revealed that rsFC between the left thalamus and the frontal pole/inferior frontal gyrus was significantly correlated with ∆LSAS (adjusted R2 = 0.65; p = 0.00002). Compared with HCs, the pre-CT patients had higher rsFCs between the thalamus and temporal pole and between the thalamus and superior/middle temporal gyrus/planum temporale (p < 0.05). The rsFC between the thalamus and the frontal pole decreased post-CT (p < 0.05). Conclusion: SAD patients had significant rsFC between the thalamus and temporal pole, superior/middle temporal gyrus, and planum temporale, which may be indicators of extreme anxiety in social situations. In addition, rsFC between the thalamus and the frontal pole may be a neuromarker for the effectiveness of individual CT.

Separating neuronal activity and systemic low-frequency oscillation related BOLD responses at nodes of the default mode network during resting-state fMRI with multiband excitation echo-planar imaging.

Functional magnetic resonance imaging (fMRI) evaluates brain activity using blood oxygenation level-dependent (BOLD) contrast. Resting-state fMRI (rsfMRI) examines spontaneous brain function using BOLD in the absence of a task, and the default mode network (DMN) has been identified from that. The DMN is a set of nodes within the brain that appear to be active and in communication when the subject is in an awake resting state. In addition to signal changes related to neural activity, it is thought that the BOLD signal may be affected by systemic low-frequency oscillations (SysLFOs) that are non-neuronal in source and likely propagate throughout the brain to arrive at different regions at different times. However, it may be difficult to distinguish between the response due to neuronal activity and the arrival of a SysLFO in specific regions. Conventional single-shot EPI (Conv) acquisition requires a longish repetition time, but faster image acquisition has recently become possible with multiband excitation EPI (MB). In this study, we evaluated the time-lag between nodes of the DMN using both Conv and MB protocols to determine whether it is possible to distinguish between neuronal activity and SysLFO related responses during rsfMRI. While the Conv protocol data suggested that SysLFOs substantially influence the apparent time-lag of neuronal activity, the MB protocol data implied that the effects of SysLFOs and neuronal activity on the BOLD response may be separated. Using a higher time-resolution acquisition for rsfMRI might help to distinguish neuronal activity induced changes to the BOLD response from those induced by non-neuronal sources.

Super-resolution generative adversarial networks with static T2*WI-based subject-specific learning to improve spatial difference sensitivity in fMRI activation.

The spatial resolution of fMRI is relatively poor and improvements are needed to indicate more specific locations for functional activities. Here, we propose a novel scheme, called Static T2*WI-based Subject-Specific Super Resolution fMRI (STSS-SRfMRI), to enhance the functional resolution, or ability to discriminate spatially adjacent but functionally different responses, of fMRI. The scheme is based on super-resolution generative adversarial networks (SRGAN) that utilize a T2*-weighted image (T2*WI) dataset as a training reference. The efficacy of the scheme was evaluated through comparison with the activation maps obtained from the raw unpreprocessed functional data (raw fMRI). MRI images were acquired from 30 healthy volunteers using a 3 Tesla scanner. The modified SRGAN reconstructs a high-resolution image series from the original low-resolution fMRI data. For quantitative comparison, several metrics were calculated for both the STSS-SRfMRI and the raw fMRI activation maps. The ability to distinguish between two different finger-tapping tasks was significantly higher [p = 0.00466] for the reconstructed STSS-SRfMRI images than for the raw fMRI images. The results indicate that the functional resolution of the STSS-SRfMRI scheme is superior, which suggests that the scheme is a potential solution to realizing higher functional resolution in fMRI images obtained using 3T MRI.

Quantitative measurement of diffusion-weighted imaging signal using expression-controlled aquaporin-4 cells: Comparative study of 2-compartment and diffusion kurtosis imaging models.

The purpose of this study was to compare parameter estimates for the 2-compartment and diffusion kurtosis imaging models obtained from diffusion-weighted imaging (DWI) of aquaporin-4 (AQP4) expression-controlled cells, and to look for biomarkers that indicate differences in the cell membrane water permeability. DWI was performed on AQP4-expressing and non-expressing cells and the signal was analyzed with the 2-compartment and diffusion kurtosis imaging models. For the 2-compartment model, the diffusion coefficients (Df, Ds) and volume fractions (Ff, Fs, Ff = 1-Fs) of the fast and slow compartments were estimated. For the diffusion kurtosis imaging model, estimates of the diffusion kurtosis (K) and corrected diffusion coefficient (D) were obtained. For the 2-compartment model, Ds and Fs showed clear differences between AQP4-expressing and non-expressing cells. Fs was also sensitive to cell density. There was no clear relationship with the cell type for the diffusion kurtosis imaging model parameters. Changes to cell membrane water permeability due to AQP4 expression affected DWI of cell suspensions. For the 2-compartment and diffusion kurtosis imaging models, Ds was the parameter most sensitive to differences in AQP4 expression.

Distribution of intraperitoneally administered deuterium-labeled water in aquaporin-4-knockout mouse brain after middle cerebral artery occlusion.

Introduction: As the movement of water in the brain is known to be involved in neural activity and various brain pathologies, the ability to assess water dynamics in the brain will be important for the understanding of brain function and the diagnosis and treatment of brain diseases. Aquaporin-4 (AQP4) is a membrane channel protein that is highly expressed in brain astrocytes and is important for the movement of water molecules in the brain. Methods: In this study, we investigated the contribution of AQP4 to brain water dynamics by administering deuterium-labeled water (D2O) intraperitoneally to wild-type and AQP4 knockout (AQP4-ko) mice that had undergone surgical occlusion of the middle cerebral artery (MCA). Water dynamics in the infarct region and on either side of the anterior cerebral artery (ACA) was monitored with proton-density-weighted imaging (PDWI) performed on a 7T animal MRI. Results: D2O caused a negative signal change quickly after administration. The AQP4-ko mice showed a delay of the time-to-minimum in both the contralateral and ipsilateral ACA regions compared to wild-type mice. Also, only the AQP4- ko mice showed a delay of the time-to-minimum in the ipsilateral ACA region compared to the contralateral side. In only the wild-type mice, the signal minimum in the ipsilateral ACA region was higher than that in the contralateral ACA region. In the infarct region, the signal attenuation was slower for the AQP4-ko mice in comparison to the wild-type mice. Discussion: These results suggest that AQP4 loss affects water dynamics in the ACA region not only in the infarct region. Dynamic PDWI after D2O administration may be a useful tool for showing the effects of AQP4 in vivo.

Exploring cell membrane water exchange in aquaporin-4-deficient ischemic mouse brain using diffusion-weighted MRI.

BACKGROUND: Aquaporin-4 is a membrane channel protein that is highly expressed in brain astrocytes and facilitates the transport of water molecules. It has been suggested that suppression of aquaporin-4 function may be an effective treatment for reducing cellular edema after cerebral infarction. It is therefore important to develop clinically applicable measurement systems to evaluate and better understand the effects of aquaporin-4 suppression on the living body. METHODS: Animal models of focal cerebral ischemia were created by surgically occluding the middle cerebral artery of wild-type and aquaporin-4 knockout mice, after which multi-b-value multi-diffusion-time diffusion-weighted imaging measurements were performed. Data were analyzed with both the apparent diffusion coefficient (ADC) model and a compartmental water-exchange model. RESULTS: ADCs were estimated for five different b value ranges. The ADC of aquaporin-4 knockout mice in the contralateral region was significantly higher than that of wild-type mice for each range. In contrast, aquaporin-4 knockout mice had significantly lower ADC than wild-type mice in ischemic tissue for each b-value range. Genotype-dependent differences in the ADC were particularly significant for the lowest ranges in normal tissue and for the highest ranges in ischemic tissue. The ADCs measured at different diffusion times were significantly different for both genotypes. Fitting of the water-exchange model to the ischemic region data found that the water-exchange time in aquaporin-4 knockout mice was approximately 2.5 times longer than that in wild-type mice. CONCLUSIONS: Multi-b-value multi-diffusion-time diffusion-weighted imaging may be useful for in vivo research and clinical diagnosis of aquaporin-4-related diseases.

Longitudinal stability of a multimodal visco-elastic polyacrylamide gel phantom for magnetic resonance and ultrasound shear-wave elastography.

We evaluated the long-term stability of a newly developed viscoelastic phantom made of polyacrylamide (PAAm) gel for magnetic resonance elastography (MRE) and ultrasound-based shear-wave elastography (US SWE). The stiffness of the cylindrical phantom was measured at 0, 13 and 18 months. Storage and loss moduli were measured with MRE, and shear-wave speed (SWS) was measured with US SWE. Long-term stability was evaluated in accordance with the Quantitative Imaging Biomarker Alliance (QIBA) profiles for each modality. The initial storage and loss moduli of the phantom were 5.01±0.22 and 1.11±0.15 respectively, and SWS was 2.57±0.04 m/s. The weight of the phantom decreased by 0.6% over the 18 months. When measured with MRE, the stiffness of the phantom decreased and changes to the storage and loss moduli were -3.0% and -4.6% between 0 and 13 months, and -4.3% and 0.0% between 0 and 18 months. The US measurements found that SWS decreased by 2.4% over the first 13 months and 3.6% at 18 months. These changes were smaller than the tolerances specified in the QIBA profiles, so the viscoelastic PAAm gel phantom fulfilled the condition for long-term stability. This new phantom has the potential to be used as a quality assurance and quality control phantom for MRE and US SWE.

Oscillating-gradient spin-echo diffusion-weighted imaging (OGSE-DWI) with a limited number of oscillations: I. Signal equation.

The oscillating-gradient spin-echo (OGSE) sequence has been promoted as a promising diffusion-weighted magnetic resonance imaging (DWI) technique for probing in vivo tissue microstructure in the frequency domain. However, due to practical restrictions on the duration and number of oscillations that a motion-probing gradient can have, the technique has limited spectral resolution and range. This work re-examines the OGSE-DWI method to clarify how these limitations are reflected in the signal model. There are several aspects of the revised framework that distinguish it from the conventional description employed for OGSE DWI. In particular, while the conventional OGSE signal model implies that the spectral density of molecular diffusion may be directly sampled in experiments, in practice information about the spectral density can be only indirectly obtained.

White matter changes following experimental pediatric traumatic brain injury: an advanced diffusion-weighted imaging investigation.

Pediatric traumatic brain injury (pTBI) is a major community health concern. Due to ongoing maturation, injury to the brain at a young age can have devastating consequences in later life. However, how pTBI affects brain development, including white matter maturation, is still poorly understood. Here, we used advanced diffusion weighted imaging (DWI) to assess chronic white matter changes after experimental pTBI. Mice at post-natal day 21 sustained a TBI using the controlled cortical impact model and magnetic resonance imaging (MRI) was performed at 6 months post-injury using a 4.7 T Bruker scanner. Four diffusion shells with 81 directions and b-values of 1000, 3000, 5000, and 7000s/mm2 were acquired and analyzed using MRtrix3 software. Advanced DWI metrics, including fiber density, fiber cross-section and a combined fiber density and cross-section measure, were investigated together with three track-weighted images (TWI): the average pathlength map, mean curvature and the track density image. These advanced metrics were compared to traditional diffusion tensor imaging (DTI) metrics which indicated that TBI injured mice had reduced fractional anisotropy and increased radial diffusivity in the white matter when compared to age-matched sham controls. Consistent with previous findings, fiber density and TWI metrics appeared to be more sensitive to white matter changes than DTI metrics, revealing widespread reductions in fiber density and TWI metrics in pTBI mice compared to sham controls. These results provide additional support for the use of advanced DWI metrics in assessing white matter degeneration following injury and highlight the chronic outcomes that can follow pTBI.

Hydraulic distension as a treatment for patellofemoral pain syndrome (PFPS) non-responsive to standard rehabilitation.

BACKGROUND: The occurrence of Patellofemoral Pain Syndrome (PFPS) is often found in daily medical care. Rehabilitation is usually applied with good results. However, patients often do not respond to standard rehabilitation, suggesting there may be some undetected factors that standard treatments cannot address. It is known that post-traumatic adhesive capsulitis in the knee often shows symptoms similar to those of PFPS, but idiopathic adhesive capsulitis (IAC) has seldom been mentioned as a possible cause of PFPS. Adhesive capsulitis in the shoulder joint causes frozen shoulder (FS), and hydraulic distension (HD) is often applied to FS effectively. PURPOSE: The purpose of this study was to investigate and report on the clinical application of HD to treat PFPS non-responsive to rehabilitation treatment. PATIENTS AND METHODS: HD was applied to 72 knees that had resisted regular conservative treatments for PFPS. Follow-up data (e.g. visual analogue scale) was collected immediately after HD, and at periods of 1, 3 and 6 months later. RESULTS: Of the 72 patients, 64 patients obtained pain relief after HD. Pain was relieved for at least 6 months for 33 of the 64 patients. No benefit was received for 8 patients. CONCLUSIONS: HD could be an additional conservative option for some PFPS that resisted rehabilitation. Assuming that the mechanisms of action for HD in the knee are the same as those in FS, there is evidence to suggest that IAC might play a role in the development of PFPS for some patients.

The Utility of a Convolutional Neural Network for Generating a Myelin Volume Index Map from Rapid Simultaneous Relaxometry Imaging.

PURPOSE: A current algorithm to obtain a synthetic myelin volume fraction map (SyMVF) from rapid simultaneous relaxometry imaging (RSRI) has a potential problem, that it does not incorporate information from surrounding pixels. The purpose of this study was to develop a method that utilizes a convolutional neural network (CNN) to overcome this problem. METHODS: RSRI and magnetization transfer images from 20 healthy volunteers were included. A CNN was trained to reconstruct RSRI-related metric maps into a myelin volume-related index (generated myelin volume index: GenMVI) map using the MVI map calculated from magnetization transfer images (MTMVI) as reference. The SyMVF and GenMVI maps were statistically compared by testing how well they correlated with the MTMVI map. The correlations were evaluated based on: (i) averaged values obtained from 164 atlas-based ROIs, and (ii) pixel-based comparison for ROIs defined in four different tissue types (cortical and subcortical gray matter, white matter, and whole brain). RESULTS: For atlas-based ROIs, the overall correlation with the MTMVI map was higher for the GenMVI map than for the SyMVF map. In the pixel-based comparison, correlation with the MTMVI map was stronger for the GenMVI map than for the SyMVF map, and the difference in the distribution for the volunteers was significant (Wilcoxon sign-rank test, P < 0.001) in all tissue types. CONCLUSION: The proposed method is useful, as it can incorporate more specific information about local tissue properties than the existing method. However, clinical validation is necessary.

Imaging of Hypoxic Tumor: Correlation between Diffusion-weighted MR Imaging and 18F-fluoroazomycin Arabinoside Positron Emission Tomography in Head and Neck Carcinoma.

We investigated the usefulness of diffusion-weighted imaging (DWI) for detecting changes in the structure of hypoxic cells by evaluating the correlation between 18F-fluoroazomycin arabinoside (FAZA) positron emission tomography activity and DWI parameters in head and neck carcinoma. The diffusion coefficient corresponding to the slow compartment of a two-compartment model had a significant positive correlation with FAZA activity (ρ = 0.58, P = 0.016), whereas the diffusional kurtosis from diffusion kurtosis imaging had a significant negative correlation (ρ = -0.62, P = 0.008), which suggests that those DWI parameters might be useful as indicators for changes in cell structure.

The Utility of Applying Various Image Preprocessing Strategies to Reduce the Ambiguity in Deep Learning-based Clinical Image Diagnosis.

PURPOSE: A general problem of machine-learning algorithms based on the convolutional neural network (CNN) technique is that the reason for the output judgement is unclear. The purpose of this study was to introduce a strategy that may facilitate better understanding of how and why a specific judgement was made by the algorithm. The strategy is to preprocess the input image data in different ways to highlight the most important aspects of the images for reaching the output judgement. MATERIALS AND METHODS: T2-weighted brain image series falling into two age-ranges were used. Classifying each series into one of the two age-ranges was the given task for the CNN model. The images from each series were preprocessed in five different ways to generate five different image sets: (1) subimages from the inner area of the brain, (2) subimages from the periphery of the brain, (3-5) subimages of brain parenchyma, gray matter area, and white matter area, respectively, extracted from the subimages of (2). The CNN model was trained and tested in five different ways using one of these image sets. The network architecture and all the parameters for training and testing remained unchanged. RESULTS: The judgement accuracy achieved by training was different when the image set used for training was different. Some of the differences was statistically significant. The judgement accuracy decreased significantly when either extra-parenchymal or gray matter area was removed from the periphery of the brain (P < 0.05). CONCLUSION: The proposed strategy may help visualize what features of the images were important for the algorithm to reach correct judgement, helping humans to understand how and why a particular judgement was made by a CNN.

Intra- and inter-operator reproducibility of US point shear-wave elastography in various organs: evaluation in phantoms and healthy volunteers.

PURPOSE: This study was conducted in order to assess the intra- and interoperator reproducibility of shear-wave speed (SWS) measurement on elasticity phantoms and healthy volunteers using ultrasound-based point shear-wave elastography. MATERIALS AND METHODS: This study was approved by the institutional review board. Two operators measured the SWS of five elasticity phantoms and seven organs (thyroid, lymph node, muscle, spleen, kidney, pancreas, and liver) of 30 healthy volunteers with 1.0-4.5 MHz convex (4C1) and 4.0-9.0 MHz linear (9L4) transducers. The phantom measurements were repeated ten times, while the volunteer measurements were performed five times each. Intra- and interoperator reproducibility was assessed. Interoperator reproducibility was also evaluated with the 95% Bland-Altman limits of agreement (LOA). RESULTS: In phantoms, all intraclass correlation coefficients (ICCs) were above 0.90 and the 95% LOA between the two operators were less than ± 18%. In volunteers, intraoperator ICCs were > 0.75 for all regions except the pancreas. Interoperator ICC was above 0.75 for the right lobe of the liver (depth 4 cm) and the kidney, but the 95% LOA was less than ± 25% only for the liver. CONCLUSION: Although excellent in phantoms, interoperator reproducibility was insufficient for all regions in the volunteers other than the right hepatic lobe at a depth of 4 cm. Clinicians should be aware of the 95% LOA when using SWS in patients. KEY POINTS: • Our phantom study indicated a high reproducibility for shear-wave speed (SWS) measurements with point shear-wave elastography (pSWE). • In volunteers, intraoperator reproducibility was generally high, but the interoperator reproducibility was not high enough except for the right hepatic lobe at 4 cm depth. • To evaluate interoperator reproducibility, the 95% limits of agreement (LOA) between operators should be considered in addition to the intraclass correlation coefficient (ICC).

Comparison of diffusion-weighted MRI and anti-Stokes Raman scattering (CARS) measurements of the inter-compartmental exchange-time of water in expression-controlled aquaporin-4 cells.

We performed multi-b and multi-diffusion-time diffusion-weighted magnetic resonance imaging on aquaporin-4-expressing (AQ) and -non-expressing (noAQ) cells, and demonstrated a clear difference between the signals from the two cell types. The data were interpreted using a two-compartment (intra and extracellular spaces) model including inter-compartmental exchange. It was also assumed that restricted diffusion of water molecules inside the cells leads to the intracellular diffusion coefficient being inversely proportional to the diffusion-time. Estimates of the water-exchange-times obtained with this model are compared to those measured using an independent optical imaging technique (coherent anti-Stokes Raman scattering imaging, CARS). For both techniques it was found that the exchange-time estimated for the noAQ cells was significantly longer than that for the AQ cells.

Water Diffusion in the Brain of Chronic Hypoperfusion Model Mice: A Study Considering the Effect of Blood Flow.

PURPOSE: Chronic cerebral hypoperfusion model mice were created by unilateral common carotid artery occlusion (UCCAO) surgery, which does not cause cerebral infarction, but which does cause long-term reduction in cerebral blood flow (CBF) to the occluded side. Cognitive dysfunction in this mouse model has been demonstrated in behavioral experiments, but neuron density change was not found in a previous positron emission tomography (PET) study. As a next step, in this study we investigated the injury of neuronal fibers in chronic cerebral hypoperfusion model mice using diffusion tensor imaging (DTI). METHODS: In diffusion-weighted imaging (DWI), not only the diffusion of water but also the capillary flow in the voxel, i.e., intravoxel incoherent motion (IVIM), contributes to the signal. Thus, we used DTI to evaluate DWI signal changes in the brains of chronic hypoperfusion model mice at 4 weeks after UCCAO while monitoring the possible influence of CBF change using arterial spin-labeling (ASL) MRI. RESULTS: Simple t-tests indicated that there were significant differences in CBF between the control and occluded sides of the brain, but there was no significant difference for the mean diffusivity (MD) or fractional anisotropy (FA). However, as Pearson correlation analysis showed that MD was strongly correlated with CBF, analysis-of-covariance (ANCOVA) was then performed using CBF as a covariate and a significant difference in MD between the contra- and ipsilateral sides was found. Performing a similar procedure for the FA found no significant differences. CONCLUSION: The results suggest the injury of neuronal fibers due to chronic hypoperfusion. It is also suggested that CBF-related signal changes should be considered when DWI-based information is used for pathological diagnosis.

Comparison of Glass Capillary Plates and Polyethylene Fiber Bundles as Phantoms to Assess the Quality of Diffusion Tensor Imaging.

PURPOSE: The purpose of this study was to evaluate the suitability of two phantoms, one made of capillary plates and the other polyethylene fibers, for assessing the quality of diffusion tensor imaging (DTI). METHODS: The first phantom was a stack of glass capillary plates with many parallel micropores (CP). The second phantom was a bundle of polyethylene fiber Dyneema held together with a thermal shrinkage tube (Dy). High resolution multi-shot echo planar imaging (EPI) DTI acquisitions were performed at b-values of 0 and 1000 s/mm2 and diffusion-times (Tdiff) of 37.7 and 97.7 ms on a preclinical 7T MRI scanner. Thirty diffusion-encoding directions were used. The data were used to calculate the fractional anisotropy (FA), mean diffusivity (MD), and angular dispersion (AD). Further acquisitions were performed at b-values from 0 to 8000 s/mm2 in 14 steps with the diffusion gradient applied parallel (axial) and perpendicular (radial) to the Z direction. On the other hand, the data acquired with a 3T MRI scanner were used to confirm that measurements on a clinical machine are consistent with the 7T MRI results. RESULTS: The dependence of FA, MD and AD on Tdiff was smaller for the Dy than for the CPs. The b-value-dependent signal attenuations in the axial direction at Tdiff = 37.7 and 97.7 ms were similar for both phantoms. In the radial direction, Dy demonstrated similar b-value attenuation to that of in vivo tissue for both Tdiffs, but the attenuation for the CPs was affected by the change in Tdiff. Parameter estimates were similar for 3T and 7T MRI. CONCLUSION: The characteristics of the CP indicate that it can be used as a restricted-diffusion dominant phantom, while the characteristics of the Dy suggest that it can be used as a hindered-diffusion dominant phantom. Dy may be more suitable than CP for DTI quality control.

Evaluation of a combination tumor treatment using thermo-triggered liposomal drug delivery and carbon ion irradiation.

The combination of radiotherapy with chemotherapy is one of the most promising strategies for cancer treatment. Here, a novel combination strategy utilizing carbon ion irradiation as a high-linear energy transfer (LET) radiotherapy and a thermo-triggered nanodevice is proposed, and drug accumulation in the tumor and treatment effects are evaluated using magnetic resonance imaging relaxometry and immunohistology (Ki-67, n = 15). The thermo-triggered liposomal anticancer nanodevice was administered into colon-26 tumor-grafted mice, and drug accumulation and efficacy was compared for 6 groups (n = 32) that received or did not receive the radiotherapy and thermo trigger. In vivo quantitative R1 maps visually demonstrated that the multimodal thermosensitive polymer-modified liposomes (MTPLs) can accumulate in the tumor tissue regardless of whether the region was irradiated by carbon ions or not. The tumor volume after combination treatment with carbon ion irradiation and MTPLs with thermo-triggering was significantly smaller than all the control groups at 8 days after treatment. The proposed strategy of combining high-LET irradiation and the nanodevice provides an effective approach for minimally invasive cancer treatment.

Changes in Apparent Fiber Density and Track-Weighted Imaging Metrics in White Matter following Experimental Traumatic Brain Injury.

Traumatic brain injury (TBI) has been assessed with diffusion tensor imaging (DTI), a commonly used magnetic resonance imaging (MRI) marker for white matter integrity. However, given that the DTI model only fits a single fiber orientation, results can become confounded in regions of "crossing" white matter fibers. In contrast, constrained spherical deconvolution estimates a fiber orientation distribution directly from high angular resolution diffusion-weighted images. Consequently, constrained spherical deconvolution-based measures, such as apparent fiber density (AFD) and track-weighted imaging (TWI) metrics (including tract density imaging, average pathlength mapping, and mean curvature), may be more sensitive than DTI metrics to white matter injury post-TBI. As such, this study administered the lateral fluid percussion injury (FPI) model of TBI, assessed for changes in AFD and TWI metrics, and compared these results to the DTI metrics, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). Rats received either an FPI (n = 11) or sham injury (n = 9) and after a recovery period of 12 weeks underwent MRI. AFD was calculated as described previously and statistical testing was performed using connectivity-based fixel enhancement. TWI and DTI metrics were assessed using voxel-wise nonparametric permutation testing. We found that rats given an FPI had significantly reduced AFD, tract density, average pathlength, and mean curvature when compared to sham-injured rats and significant changes in DTI metrics, including reduced FA and increased MD, RD, and AD. However, the latter DTI metrics identified fewer voxels affected by TBI. Additionally, analysis of AFD with connectivity-based fixel enhancement was the only method that identified damage within the corticospinal tract of rats given an FPI. These results support the use of constrained spherical deconvolution, in conjunction with DTI metrics, to better assess disease progression and treatment post-TBI.

Principal Component Analysis of Multimodal Neuromelanin MRI and Dopamine Transporter PET Data Provides a Specific Metric for the Nigral Dopaminergic Neuronal Density.

The loss of dopaminergic (DA) neurons in the substantia nigra (SN) is a major pathophysiological feature of patients with Parkinson's disease (PD). As nigral DA neurons contain both neuromelanin (NM) and dopamine transporter (DAT), decreased intensities in both NM-sensitive MRI and DAT PET reflect decreased DA neuronal density. This study demonstrates that a more specific metric for the nigral DA neuronal density can be derived with multimodal MRI and PET. Participants were 11 clinically diagnosed PD patients and 10 age and gender matched healthy controls (HCs). Two quantities, the NM-related index (RNM) and the binding potential of the radiotracer [18F]FE-PE2I to DAT (BPND) in SN, were measured for each subject using MRI and PET, respectively. Principal component analysis (PCA) was applied to the multimodal data set to estimate principal components. One of the components, PCP, corresponds to a basis vector oriented in a direction where both BPND and RNM increase. The ability of BPND, RNM and PCP to discriminate between HC and PD groups was compared. Correlation analyses between the motor score of the unified Parkinson's disease rating scale and each metric were also performed. PCP, BPND and RNM for PD patients were significantly lower than those for HCs (F = 16.26, P<0.001; F = 6.05, P = 0.008; F = 7.31, P = 0.034, respectively). The differential diagnostic performance between the HC and PD groups as assessed by the area under the receiver-operating characteristic curve was best for PCP (0.94, 95% CI: 0.66-1.00). A significant negative correlation was found between the motor severity score and PCp (R = -0.70, P<0.001) and RNM (R = -0.52, P = 0.015), but not for BPND (R = -0.36, P = 0.110). PCA of multimodal NM-sensitive MRI and DAT PET data provides a metric for nigral DA neuronal density that will help illuminate the pathophysiology of PD in SN. Further studies are required to explore whether PCA is useful for other parkinsonian syndromes.