Impact of region-of-interest method on quantitative analysis of DTI data in the optic tracts.

BACKGROUND: To extract DTI parameters from a specific structure, a region of interest (ROI) must be defined. ROI selection in small structures is challenging; the final measurement results could be affected due to the significant impact of small geometrical errors. In this study the optic tracts were analyzed with the aim to assess differences in DTI parameters due to ROI method and to identify the most reliable method. METHODS: Images of 20 healthy subjects were acquired. Fractional anisotropy (FA) was extracted from the optic tracts by four different ROI methods. Manual tracing was performed in 1) the b0 image and 2) a T1-weighted image registered to the FA image. Semi-automatic segmentation was performed based on 3) tractography and 4) the FA-skeleton algorithm in the tract-based spatial statistics (TBSS) framework. Results were analyzed with regard to ROI method as well as to inter-scan, intra-rater and inter-rater reliability. RESULTS: The resulting FA values divided the ROI methods into two groups that differed significantly: 1) the FA-skeleton and the b0 methods showed higher FA values compared to 2) the tractography and the T1-weighted methods. The intra- and inter-rater variabilities were similar for all methods, except for the tractography method where the inter-rater variability was higher. The FA-skeleton method had a better reproducibility than the other methods. CONCLUSION: Choice of ROI method was found to be highly influential on FA values when the optic tracts were analyzed. The FA-skeleton method performed the best, yielding low variability and high repeatability.

Tractography of Meyer's loop for temporal lobe resection­validation by prediction of postoperative visual field outcome‬‬‬‬.

BACKGROUND: Postoperative visual field defects are common after temporal lobe resection because of injury to the most anterior part of the optic radiation, Meyer's loop. Diffusion tensor tractography is a promising technique for visualizing the optic radiation preoperatively. The aim of this study was to assess the anatomical accuracy of Meyer's loop, visualized by the two most common tractography methods­deterministic (DTG) and probabilistic tractography (PTG)­in patients who had undergone temporal lobe resection. METHODS: Eight patients with temporal lobe resection for temporal lobe pathology were included. Perimetry and diffusion tensor imaging were performed pre- and postoperatively. Two independent operators analyzed the distance between the temporal pole and Meyer's loop (TP-ML) using DTG and PTG. Results were compared to each other, to data from previously published dissection studies and to postoperative perimetry results. For the latter, Spearman's rank correlation coefficient (r(s)) was used. RESULTS: Median preoperative TP-ML distances for nonoperated sides were 42 and 35 mm, as determined by DTG and PTG, respectively. TP-ML assessed with PTG was a closer match to dissection studies. Intraclass correlation coefficients were 0.4 for DTG and 0.7 for PTG. Difference between preoperative TP-ML (by DTG and PTG, respectively) and resection length could predict the degree of postoperative visual field defects (DTG: r(s) = -0.86, p < 0.05; PTG: r(s) = -0.76, p < 0.05). CONCLUSION: Both DTG and PTG could predict the degree of visual field defects. However, PTG was superior to DTG in terms of reproducibility and anatomical accuracy. PTG is thus a strong candidate for presurgical planning of temporal lobe resection that aims to minimize injury to Meyer's loop.

Ketoconazole-associated preferential increase in dopamine D2 receptor occupancy in striatum compared to pituitary in vivo: role for drug transporters?

Membrane transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are efflux pumps that remove drugs from the brain back to the peripheral blood compartment, serving as a functional component of the blood-brain barrier (BBB). We report here that coadministration of the P-gp and BCRP inhibitor ketoconazole with risperidone may preferentially increase D2 receptor occupancy in the striatum compared to pituitary. Four male patients with schizophrenia or schizoaffective disorder who had received at least 4 prior injections of the long-acting risperidone at a stable dose of 25 to 50 mg participated in this positron emission tomography study. Multiple-dose ketoconazole coadministration reduced the P-gp activity as shown by fexofenadine oral challenge. Importantly, we found a strong statistical trend in this sample of 4 subjects who consistently showed a decrease in striatal fluorine 18 (F)-fallypride binding (an indication of increased D2 receptor occupancy) after ketoconazole coadministration (P = 0.057), whereas the pituitary (a region that lies outside the BBB) F-fallypride binding did not change (P = 0.99). These observations warrant further research with selective drug transporter inhibitors. We suggest that in neuroimaging studies, the pituitary drug occupancy can serve as a useful new "positive control" to evaluate whether drug occupancy is preferentially increased in brain regions that fall inside the BBB after cotreatment with P-gp and BCRP inhibitors. This is a noteworthy study design consideration regarding the future clinical testing of novel adjunct interventions aimed at modulating membrane transporter function at the BBB, with the goal of augmenting drug access into the brain compartment, particularly in treatment-resistant psychiatric illness.

Visual pathway impairment by pituitary adenomas: quantitative diagnostics by diffusion tensor imaging.

OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas, little is known about objective indices that may reveal risk of visual impairment caused by tumor growth that leads to compression of the anterior visual pathways. This study aimed to explore diffusion tensor imaging (DTI) as a means for objective assessment of injury to the anterior visual pathways caused by pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas, scheduled for transsphenoidal tumor resection, and 20 healthy control subjects were included in the study. A minimum suprasellar tumor extension of Grade 2-4, according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and posterior) scale, was required for inclusion. Neuroophthalmological examinations, conventional MRI, and DTI were completed in all subjects and were repeated 6 months after surgery. Quantitative assessment of chiasmal lift, visual field defect (VFD), and DTI parameters from the optic tracts was performed. Linear correlations, group comparisons, and prediction models were done in controls and patients. RESULTS Both the degree of VFD and chiasmal lift were significantly correlated with the radial diffusivity (r = 0.55, p < 0.05 and r = 0.48, p < 0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = -0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial diffusivity differed significantly between controls and patients with VFD, both before and after surgery (p < 0.05); however, no difference was found between patients with and without VFD. Based on the axial diffusivity and fractional anisotropy, a prediction model classified all patients with VFD correctly (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and 17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect pathology and degree of injury in the anterior visual pathways that were compressed by pituitary adenomas. The correlation between radial diffusivity and visual impairment may reflect a gradual demyelination in the visual pathways caused by an increased tumor effect. The low level of axial diffusivity found in the patient group may represent early atrophy in the visual pathways, detectable on DTI but not by conventional methods. DTI may provide objective data, detect early signs of injury, and be an additional diagnostic tool for determining indication for surgery in cases of pituitary adenomas.

Strengths and limitations of tractography methods to identify the optic radiation for epilepsy surgery.

Diffusion tensor imaging (DTI) tractography (TG) can visualize Meyer's loop (ML), providing important information for the epilepsy surgery team, both for preoperative counseling and to reduce the frequency of visual field defects after temporal lobe resection (TLR). This review highlights significant steps in the TG process, specifically the processing of raw data including choice of TG algorithm and the interpretation and validation of results. A lack of standardization of TG of the optic radiation makes study comparisons challenging. We discuss results showing differences between studies and uncertainties large enough to be of clinical relevance and present implications of this technique for temporal lobe epilepsy surgery. Recent studies in temporal lobe epilepsy patients, employing TG intraoperatively, show promising results in reduction of visual field defects, with maintained seizure reduction.

Visualizing Meyer's loop: A comparison of deterministic and probabilistic tractography.

BACKGROUND: Diffusion tensor tractography of the anterior extent of the optic radiation - Meyer's loop - prior to temporal lobe resection (TLR) may reduce the risk for postoperative visual field defect. Currently there is no standardized way to perform tractography. OBJECTIVE: To visualize Meyer's loop using deterministic (DTG) and probabilistic tractography (PTG) at different probability levels, with the primary aim to explore possible differences between methods, and the secondary aim to explore anatomical accuracy. METHODS: Twenty-three diffusion tensor imaging exams (11 controls and 7 TLR-patients, pre- and post-surgical) were analyzed using DTG and PTG thresholded at probability levels 0.2%, 0.5%, 1%, 5% and 10%. The distance from the tip of the temporal lobe to the anterior limit of Meyer's loop (TP-ML) was measured in 46 optic radiations. Differences in TP-ML between the methods were compared. Results of the control group were compared to dissection studies and to a histological atlas. RESULTS: For controls and patients together, there were statistically significant differences (p<0.01) for TP-ML between all methods thresholded at PTG ≤1% compared to all methods thresholded at PTG ≥5% and DTG. There were no statistically significant differences between PTG 0.2%, 0.5% and 1% or between PTG 5%, 10% and DTG. For the control group, PTG ≤1% showed a closer match to dissection studies and PTG 1% showed the best match to histological tracings of Meyer's loop. CONCLUSIONS: Choice of tractography method affected the visualized location of Meyer's loop significantly in a heterogeneous, clinically relevant study group. For the controls, PTG at probability levels ≤1% was a closer match to dissection studies. To determine the anterior extent of Meyer's loop, PTG is superior to DTG and the probability level of PTG matters.

On high order tensor-based diffusivity profile estimation.

Diffusion weighted magnetic resonance imaging (dMRI) is used to measure, in vivo, the self-diffusion of water molecules in biological tissues. High order tensors (HOTs) are used to model the apparent diffusion coefficient (ADC) profile at each voxel from the dMRI data. In this paper we propose: (i) A new method for estimating HOTs from dMRI data based on weighted least squares (WLS) optimization; and (ii) A new expression for computing the fractional anisotropy from a HOT that does not suffer from singularities and spurious zeros. We also present an empirical evaluation of the proposed method relative to the two existing methods based on both synthetic and real human brain dMRI data. The results show that the proposed method yields more accurate estimation than the competing methods.

Optimal diffusion tensor imaging with repeated measurements.

Several data acquisition schemes for diffusion MRI have been proposed and explored to date for the reconstruction of the 2nd order tensor. Our main contributions in this paper are: (i) the definition of a new class of sampling schemes based on repeated measurements in every sampling point; (ii) two novel schemes belonging to this class; and (iii) a new reconstruction framework for the second scheme. We also present an evaluation, based on Monte Carlo computer simulations, of the performances of these schemes relative to known optimal sampling schemes for both 2nd and 4th order tensors. The results demonstrate that tensor estimation by the proposed sampling schemes and estimation framework is more accurate and robust.