Transcranial MR Imaging-Guided Focused Ultrasound Interventions Using Deep Learning Synthesized CT.

BACKGROUND AND PURPOSE: Transcranial MR imaging-guided focused ultrasound is a promising novel technique to treat multiple disorders and diseases. Planning for transcranial MR imaging-guided focused ultrasound requires both a CT scan for skull density estimation and treatment-planning simulation and an MR imaging for target identification. It is desirable to simplify the clinical workflow of transcranial MR imaging-guided focused ultrasound treatment planning. The purpose of this study was to examine the feasibility of deep learning techniques to convert MR imaging ultrashort TE images directly to synthetic CT of the skull images for use in transcranial MR imaging-guided focused ultrasound treatment planning. MATERIALS AND METHODS: The U-Net neural network was trained and tested on data obtained from 41 subjects (mean age, 66.4 ± 11.0 years; 15 women). The derived neural network model was evaluated using a k-fold cross-validation method. Derived acoustic properties were verified by comparing the whole skull-density ratio from deep learning synthesized CT of the skull with the reference CT of the skull. In addition, acoustic and temperature simulations were performed using the deep learning CT to predict the target temperature rise during transcranial MR imaging-guided focused ultrasound. RESULTS: The derived deep learning model generates synthetic CT of the skull images that are highly comparable with the true CT of the skull images. Their intensities in Hounsfield units have a spatial correlation coefficient of 0.80 ± 0.08, a mean absolute error of 104.57 ± 21.33 HU, and a subject-wise correlation coefficient of 0.91. Furthermore, deep learning CT of the skull is reliable in the skull-density ratio estimation (r = 0.96). A simulation study showed that both the peak target temperatures and temperature distribution from deep learning CT are comparable with those of the reference CT. CONCLUSIONS: The deep learning method can be used to simplify workflow associated with transcranial MR imaging-guided focused ultrasound.

Postnatal growth of the human optic nerve.

PurposeAlthough the length of the average human adult optic nerve (ON) is known, the average length of the normal full-term, newborn ON has never been adequately evaluated, nor has the in vivo growth rate of the human ON been determined. We wanted to identify both the average length of the newborn human ON and its rate of anteroposterior growth.Patients and methodsUsing MRIs from a newly generated set of normal newborn infants rescanned at 1 year, and from different aged groups, we calculated average newborn ON length and growth rate.ResultsThe newborn human ON is 25.3±0.3 mm in length from globe to chiasm, and grows by 80% in length after birth, with maximum speed of elongation occurring in the first 3 years of life, attaining full length by 15 years of age.ConclusionThe human ON grows dramatically in the first 3 years of life, and continues to grow for the first two decades. These data are relevant for pediatric treatments that may impede or alter orbital growth in infants, and maximal susceptibility to oncological procedures in early childhood.

MRI evidence that glibenclamide reduces acute lesion expansion in a rat model of spinal cord injury.

STUDY DESIGN: Experimental, controlled, animal study. OBJECTIVES: To use non-invasive magnetic resonance imaging (MRI) to corroborate invasive studies showing progressive expansion of a hemorrhagic lesion during the early hours after spinal cord trauma and to assess the effect of glibenclamide, which blocks Sur1-Trpm4 channels implicated in post-traumatic capillary fragmentation, on lesion expansion. SETTING: Baltimore. METHODS: Adult female Long-Evans rats underwent unilateral impact trauma to the spinal cord at C7, which produced ipsilateral but not contralateral primary hemorrhage. In series 1 (six control rats and six administered glibenclamide), hemorrhagic lesion expansion was characterized using MRI at 1 and 24 h after trauma. In series 2, hemorrhagic lesion size was characterized on coronal tissue sections at 15 min (eight rats) and at 24 h after trauma (eight control rats and eight administered glibenclamide). RESULTS: MRI (T2 hypodensity) showed that lesions expanded 2.3±0.33-fold (P<0.001) during the first 24 h in control rats, but only 1.2±0.07-fold (P>0.05) in glibenclamide-treated rats. Measuring the areas of hemorrhagic contusion on tissue sections at the epicenter showed that lesions expanded 2.2±0.12-fold (P<0.001) during the first 24 h in control rats, but only 1.1±0.05-fold (P>0.05) in glibenclamide-treated rats. Glibenclamide treatment was associated with significantly better neurological function (unilateral BBB scores) at 24 h in both the ipsilateral (median scores, 9 vs 0; P<0.001) and contralateral (median scores, 12 vs 2; P<0.001) hindlimbs. CONCLUSION: MRI is an accurate non-invasive imaging biomarker of lesion expansion and is a sensitive measure of the ability of glibenclamide to reduce lesion expansion.

Non-invasive electrical stimulation of the brain (ESB) modifies the resting-state network connectivity of the primary motor cortex: a proof of concept fMRI study.

An innovative method to obtain fMRI resting-state network maps during non-invasive electrical stimulation of the brain (ESB) was developed and tested. Five healthy volunteers participated in 2 fMRI sessions. In session one, a transcranial direct current stimulator (tDCS) was applied placing the positive electrode (31.5 cm(2)) over the right M1 of the cortex and the negative electrode (31.5 cm(2)) over the left supra-orbital area of the head. In session two, a monophasic pulsed current stimulator (tPCS) was applied using the identical electrode placement. Imaging was performed on a Siemens 3T Tim Trio scanner with a 12-channel head coil. At each session, five consecutive functional scans were obtained: 1) resting-state without stimulation (Rest-1), 2) a motor scan consisting of self-paced, bilateral finger-thumb opposition task, 3) resting-state with ESB (Stim-1), 4) resting-state without stimulation (Rest-2), and 5) resting-state with ESB, replicating Stim-1 (Stim-2). Data were analyzed using AFNI and MATLAB. For motor task fMRI analysis, a general linear model (GLM) determined the voxels in the right and left M1 that were significantly correlated with the motor task paradigm. The resting-state time series from the voxels in the R-M1 were averaged and the resulting time series used as a regressor in a GLM analysis to identify M1 connectivity maps. Connectivity maps were quantified as R(2) values, and then combined to give overlap maps for each of the experimental conditions. Fourier analysis determined the energy in the normalized signal average time courses extracted from L-M1 and R-M1 for each of the resting-state scans. Both tDCS and tPCS lowered the R(2) values and energy of the averaged time course in the right and left M1 ROI. The effect of the tPCS appeared more pronounced and less variable among subjects. Applying non-invasive ESB during fMRI scanning may down regulate the motor cortex's resting-state network connectivity.

Diffusion tensor MR imaging in cervical spine trauma.

BACKGROUND AND PURPOSE: Our aim was to investigate the extent and severity of changes in spinal cord diffusion tensor imaging (DTI) parameters in patients with cervical cord injury. MATERIALS AND METHODS: DTI was performed in 20 symptomatic patients (mean, 45.7 +/- 17.7 years of age; 2 women, 18 men) with cervical spine trauma and 8 volunteers (mean, 34.2 +/- 10.7 years of age; 6 men, 2 women). The whole cord and regional apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative anisotropy (RA), and volume ratio (VR) of patients and volunteers were compared. DTI parameters were calculated in 16 patients. MR imaging demonstrated hemorrhagic cord contusions (n = 6), nonhemorrhagic cord contusions (n = 4), and soft-tissue injury (n = 6). Medical records were reviewed for extent of neurologic deficit. RESULTS: Regional ADC values differed significantly between upper and mid and upper and lower (both, P < .004) cervical cord sections. FA was significantly different between upper and lower sections (P < .03). Whole cord ADC values were significantly lower in patients than in volunteers (P < .0001). Whole spine FA was not significantly decreased in patients (P < .06). ADC and FA values were significantly decreased at injury sites when compared with volunteers (P < .031 and .0001, respectively). The greatest differences in whole cord ADC, FA, RA, and VR were in patients with hemorrhagic cord contusions compared with healthy volunteers (P < .0001, .003, .0005, and .008, respectively). CONCLUSION: DTI parameters are sensitive markers of cervical cord injury, with ADC showing the greatest sensitivity. Changes in DTI parameters are most marked at injury sites and reflect the severity of cord injury.

Regional intensive and temporal patterns of functional MRI activation distinguishing noxious and innocuous contact heat.

Cortical responses to painful and nonpainful heat were measured using functional magnetic resonance imaging (fMRI) region of interest analysis (ROI) of primary somatosensory cortex (S1), secondary somatosensory cortex (S2), anterior cingulate (ACC), supplementary motor area (SMA), insula, and inferior frontal gyrus (IFG). Previous studies indicated that innocuous and noxious stimuli of different modalities produce responses with different time courses in S1 and S2. The aim of this study was to 1) determine whether temporally distinct nociceptive blood oxygen level-dependent (BOLD) responses are evoked in multiple somatosensory processing cortical areas and 2) whether these responses discriminate small noxious stimulus intensity differences. Thirty-three subjects underwent fMRI scanning while receiving three intensities of thermal stimuli, ranging from innocuous warm (41 degrees C) to 1 degrees C below tolerance, applied to the dorsum of the left foot. Innocuous and noxious responses were distinguishable in contralateral S1, the mid-ACC, and SMA. The peak of the nociceptive response was temporally delayed from the innocuous response peak by 6-8 s. Responses to noxious but not to innocuous stimuli were observed in contralateral posterior insula. Responses to innocuous and noxious stimuli were not statistically different in contralateral S2. In contralateral S1 only, the nociceptive response could differentiate heat stimuli separated by 1 degrees C. These results show that 1) multiple cortical areas have temporally distinguishable innocuous and noxious responses evoked by a painfully hot thermode, 2) the nociceptive processing properties vary across cortical regions, and 3) nociceptive responses in S1 discriminate between painful temperatures at a level unmatched in other cortical areas.

Somatotopy in human primary motor and somatosensory hand representations revisited.

High-resolution functional magnetic resonance imaging of healthy volunteers was used to study the functional anatomy of the human primary motor (M1) and somatosensory (S1) cortical hand representations during simple movements of thumb, little finger and wrist and a sequential movement of the middle three fingers. Rest served as a control state. The results demonstrated an orderly somatotopy in both M1 and S1, even though the cortical areas active with individual movements significantly overlapped. Moreover, the activation patterns in M1 and S1 differed in three aspects: (i) S1 activation was distributed into significantly more clusters than M1 and the primary cluster was smaller; (ii) the overlaps of areas active with different movements were significantly larger in M1 than in S1; (iii) the difference between the three-finger sequential movement and the single-finger movements was more pronounced in S1 than in M1. The sequence-activated S1 cortex was distributed into significantly more clusters. There was also a trend for a bigger volume difference between sequence and the single finger movements in S1 than M1. These data suggest that while the distributed character dominates in M1 and S1, a somatotopic arrangement exists for both M1 and S1 hand representations, with the S1 somatotopy being more discrete and segregated, in contrast to the more integrated and overlapping somatotopy in M1.

Influence of an optimized non-ionic emulsifier blend on properties of oil-in-water emulsions.

Properties of oil-in-water emulsions containing non-ionic emulsifiers were evaluated in relation to nature of the dispersed phase, emulsifier composition and processing parameters. Particle size of mineral oil (hydrocarbons)-in-water emulsions was independent of the HLB of an optimized emulsifier blend, whereas, the particle size of olive oil (triglycerides)-in-water emulsions was the smallest at the optimum HLB of the emulsifier blend. The non-ionic emulsifiers reduced the particle size of mineral oil emulsions more efficiently than that of olive oil emulsions. Contrary to previously published reports, the nature of the dispersed phase, HLB of the emulsifier blend or the initial particle size of emulsions showed no influence on the final particle stability of the emulsions. This difference was attributed to the optimization of the emulsifier blend and processing parameters in the preparation of emulsions.

T1-weighted three-dimensional magnetization transfer MR of the brain: improved lesion contrast enhancement.

PURPOSE: We developed and evaluated clinically T1-weighted three-dimensional gradient-echo magnetization transfer (MT) sequences for contrast-enhanced MR imaging of the brain. METHODS: A short-repetition-time, radio frequency-spoiled, 3-D sequence was developed with a 10-millisecond MT pulse at high MT power and narrow MT pulse-frequency offset, and the enhancing lesion-to-normal white matter background (L/B) and the contrast-to-noise (C/N) ratios on these images were compared with those on T1-weighted spin-echo images and on non-MT 3-D gradient-echo images in a prospective study of 45 patients with 62 enhancing lesions. In the 24 patients who had intracranial metastatic disease, the number of lesions was counted and compared on the three types of images. RESULTS: The MT ratio of normal callosal white matter was 55% on the MT 3-D gradient-echo sequences. The L/B and C/N on the MT 3-D gradient-echo images were more than double those on the 3-D gradient-echo images, and were significantly greater than those on the T1-weighted spin-echo images. In patients with metastatic disease, the MT 3-D gradient-echo images showed significantly more lesions than did the T1-weighted spin-echo or 3-D gradient-echo images. CONCLUSION: MT 3-D gradient-echo MR imaging improves the contrast between enhancing lesion and background white matter over that obtained with conventional T1-weighted 3-D gradient-echo and spin-echo imaging. MT 3-D gradient-echo imaging provides practical sampling, image coverage, and spatial resolution, attributes that may be advantageous over MT T1-weighted spin-echo techniques.

Effect of lithium on the double-quantum behavior of 23Na in normal human erythrocytes.

The double-quantum behavior of 23Na in the presence of different concentrations of Li in human erythrocytes was investigated. The 23Na double-quantum signal was quenched in both the extracellular and the intracellular compartments with increasing concentration of Li in each compartment, along with an increase in the 23Na T1 both intra- and extracellularly. Some extracellular quenching could be observed at the near therapeutic concentration of 2 mM Li. The ratio of slow to fast spin-spin (T2) relaxation times, obtained from the dependence of the double-quantum signal on creation time, approached unity at an overall Li concentration of 40 mM. These results provide evidence that Li and Na compete for both intra- and extracellular binding sites in erythrocytes.

A 7Li NMR study of visibility, spin relaxation, and transport in normal human erythrocytes.

The behavior of the lithium (Li) ion in normal human erythrocytes has been studied by 7Li NMR. The uptake of Li into the cells was followed as a function of solution conditions, temperature, hematocrit, and blood age using dysprosium tripolyphosphate shift reagent. Under our conditions the uptake of Li increases with increasing hematocrit and blood age. For packed cells the extracellular 7Li spin-lattice relaxation time was only slightly longer than the intracellular relaxation time. Thus, T1 may not be useful for separate observation of intra- and extracellular Li in vivo. The intra- and extracellular T2s were substantially shorter than the corresponding T1s. Also, the intracellular T2 was considerably shorter than that for the extracellular compartment, suggesting that T2 may provide a noninvasive handle for observation of intracellular Li. Nuclear Overhauser enhancements could be observed for both extra- and intracellular 7Li, confirming that dipolar coupling to 1H is a contributing relaxation mechanism. The 7Li NMR visibility was essentially 100% at high Li concentrations, decreasing to about 84% at 1 mM Li. Based on time course studies of the invisibility, and a comparison of NMR and inductively coupled plasma results, it appears that the invisibility of the intra- and extracellular compartments for packed cells is the same. Although a 23Na double-quantum signal could be observed for red blood cells, no double-quantum signal was observed for 7Li.