ngho Seo

Heat kernel smoothing using laplace-beltrami eigenfunctions

We present a novel surface smoothing framework using the Laplace-Beltrami eigenfunctions. The Greens function of an isotropic diffusion equation on a manifold is constructed as a linear combination of the Laplace-Beltraimi operator. The Greens function is then used in constructing heat kernel smoothing. Unlike many previous approaches, diffusion is analytically represented as a series expansion avoiding numerical instability and inaccuracy issues. This proposed framework is illustrated with mandible surfaces, and is compared to a widely used iterative kernel smoothing technique in computational anatomy. The MATLAB source code is freely available at http://brainimaging.waisman.wisc.edu/ chung/lb.

Putaminal serotonergic innervation Monitoring dyskinesia risk in Parkinson disease

Objective: To explore serotonergic innervation in the basal ganglia in relation to levodopa-induced dyskinesia in patients with Parkinson disease (PD). Methods: A total of 30 patients with PD without dementia or depression were divided into 3 matched groups (dyskinetic, nondyskinetic, and drug-naive) for this study. We acquired 2 PET scans and 3T MRI for each patient using [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (11C-DASB) and N-(3-[18F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane (18F-FP-CIT). Then we analyzed binding potentials of the 2 radiotracers at basal ganglia structures and correlations with clinical variables. Results: We observed no difference in 18F-FP-CIT binding between dyskinetic and nondyskinetic patients, whereas there were differences in 11C-DASB binding for the caudate and putamen. Binding potential ratios (11C-DASB/18F-FP-CIT) at the putamen, which indicate serotoninergic fiber innervation relative to dopaminergic fiber availability, were highest in the dyskinetic group, followed by the nondyskinetic and drug-naive PD groups. 11C-DASB/18F-FP-CIT ratios at the putamen and pallidum correlated positively with Unified Parkinsons Disease Rating Scale (UPDRS) total scores and duration of PD, and pallidal binding ratio also correlated with the UPDRS motor scores. Ratios were not dependent on dopaminergic medication dosages for any of the regions studied. Conclusions: Relative serotonergic innervation of the putamen and pallidum increased with clinical PD progression and was highest in patients with established dyskinesia. The serotonin/dopamine transporter ratio might be a potential marker of disease progression and an indicator of risk for levodopa-induced dyskinesia in PD. A prospective evaluation is warranted in the future.

Extrastriatal dopaminergic changes in Parkinson’s disease patients with impulse control disorders

Objective To investigate the extrastriatal dopaminergic neural changes in relation to the medication-related impulse control disorders (ICD) in Parkinsons disease (PD). Method A total of 31 subjects (11 and 11 drug-treated PD patients with and without medication-related ICDs and 9 healthy controls) having no other co-morbid psychiatric disorders participated in this study. Each subject underwent dynamic N-(3-[18F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography scans. Binding potentials (BP) at nucleus accumbens, amygdala, orbitofrontal and ventromedial prefrontal cortex (VMPFC), putamen and caudate nucleus were estimated, and whole brain parametric maps of [18F]-FP-CIT binding were analysed by original and putaminal normalised manners. Results Compared with the healthy controls, BPs at both VMPFCs were significantly high and the extrastriatal to putaminal BP ratios at all regions were approximately three times higher in both PD groups. The PD ICD patients showed significantly higher BPs at the right VMPFC and tendency to lower BPs at the left nucleus accumbens compared with those free of ICD. The ICD subjects also showed reduced uptakes at both ventral striatal regions in the original parametric analysis and higher uptakes at the left insular and right posterior cingulate cortex and lower uptakes at both ventral pallidums in the putaminal normalised parametric analysis compared with the non-ICD subjects. Conclusions A great gap in extrastriatal versus striatal dopaminergic fibre degenerations is an intrinsic condition predisposing to ICD in PD. Distinct pattern of extrastriatal changes between the ICD and non-ICD patients could provide a further insight into a mechanism of ICD in PD.

Laplace-Beltrami eigenfunction expansion of cortical manifolds

We represent a shape representation technique using the eigenfunctions of Laplace-Beltrami (LB) operator and compare the performance with the conventional spherical harmonic (SPHARM) representation. Cortical manifolds are represented as a linear combination of the LB-eigenfunctions, which form orthonormal basis. Since the LB-eigenfunctions reflect the intrinsic geometry of the manifolds, the new representation is supposed to more compactly represent the manifolds and outperform SPHARM representation. We demonstrate the superior reconstruction capability of the representation using cortical and amygdala surfaces as examples.

Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [(18)F]DOPA PET Study.

Some patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment-resistant schizophrenia. The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment-resistant schizophrenia. However, in this study, the treatment-resistant patients were highly symptomatic, whereas the responsive patients showed no or minimal symptoms. The study could not distinguish whether this was a trait effect or reflected the difference in symptom levels. Thus, we aimed to test whether dopaminergic function is altered in patients with a history of treatment resistance to first-line drugs relative to treatment responders when both groups are matched for symptom severity levels by recruiting treatment-resistant patients currently showed low symptom severity with the clozapine treatment. Healthy controls (n=12), patients treated with clozapine (n=12) who had not responded to first-line antipsychotics, and patients who had responded to first-line antipsychotics (n=12) were recruited. Participants were matched for age and sex and symptomatic severity level in patient groups. Participants’ dopamine synthesis capacity was measured by using [18F]DOPA PET. We found that patients treated with clozapine show lower dopamine synthesis capacity than patients who have responded to first-line treatment (Cohen’s d=0.9191 (whole striatum), 0.7781 (associative striatum), 1.0344 (limbic striatum), and 1.0189 (sensorimotor striatum) in line with the hypothesis that the dopaminergic function is linked to treatment response. This suggests that a different neurobiology may underlie treatment-resistant schizophrenia and that dopamine synthesis capacity may be a useful biomarker to predict treatment responsiveness.

MRI-Based Attenuation Correction for PET/MRI Using Multiphase Level-Set Method

Inaccuracy in MR image–based attenuation correction (MR-AC) leads to errors in quantification and the misinterpretation of lesions in brain PET/MRI studies. To resolve this problem, we proposed an improved ultrashort echo time MR-AC method that was based on a multiphase level-set algorithm with main magnetic field (B0) inhomogeneity correction. We also assessed the feasibility of this level-set–based MR-AC method (MR-AClevel), compared with CT-AC and MR-AC provided by the manufacturer of the PET/MRI scanner (MR-ACmMR). Methods: Ten healthy volunteers and 20 Parkinson disease patients underwent 18F-FDG and 18F-fluorinated-N-3-fluoropropyl-2-β-carboxymethoxy-3-β-(4-iodophenyl)nortropane (18F-FP-CIT) PET scans, respectively, using both PET/MRI and PET/CT scanners. The level-set–based segmentation algorithm automatically delimited air, bone, and soft tissue from the ultrashort echo time MR images. For the comparison, MR-AC maps were coregistered to reference CT. PET sinogram data obtained from PET/CT studies were then reconstructed using the CT-AC, MR-ACmMR, and MR-AClevel maps. The accuracies of SUV, SUVr (SUV and its ratio to the cerebellum), and specific–to–nonspecific binding ratios obtained using MR-AClevel and MR-ACmMR were compared with CT-AC using region-of-interest– and voxel-based analyses. Results: There was remarkable improvement in the segmentation of air cavities and bones and the quantitative accuracy of PET measurement using the level set. Although the striatal and cerebellar activities in 18F-FP-CIT PET and frontal activity in 18F-FDG PET were significantly underestimated by the MR-ACmMR, the MR-AClevel provided PET images almost equivalent to the CT-AC images. PET quantification error was reduced by a factor of 3 using MR-AClevel (SUV error < 10% in MR-AClevel and < 30% in MR-ACmMR [version VB18P], and < 5% in MR-AClevel and < 15% in MR-ACmMR [VB20P]). Conclusion: The results of this study indicate that our new multiphase level-set–based MR-AC method improves the quantitative accuracy of brain PET in PET/MRI studies.

Hot spots conjecture and its application to modeling tubular structures

The second eigenfunction of the Laplace-Beltrami operator follows the pattern of the overall shape of an object. This geometric property is well known and used for various applications including mesh processing, feature extraction, manifold learning, data embedding and the minimum linear arrangement problem. Surprisingly, this geometric property has not been mathematically formulated yet. This problem is directly related to the somewhat obscure hot spots conjecture in differential geometry. The aim of the paper is to raise the awareness of this nontrivial issue and formulate the problem more concretely. As an application, we show how the second eigenfunction alone can be used for complex shape modeling of tubular structures such as the human mandible.

Mandible shape modeling using the second eigenfunction of the Laplace-Beltrami operator

The second Laplace-Beltrami eigenfunction provides an intrinsic geometric way of establishing natural coordinates for elongated 3D anatomical structures obtained from medical images. The approach is used to establish the centerline of the human mandible from CT and provides automated anatomical landmarks across subjects. These landmarks are then used to quantify the growth pattern of the mandible between ages 0 and 20.

Heat kernel smoothing via laplace-beltrami eigenfunctions and its application to subcortical structure modeling

We present a new subcortical structure shape modeling framework using heat kernel smoothing constructed with the Laplace-Beltrami eigenfunctions. The cotan discretization is used to numerically obtain the eigenfunctions of the Laplace-Beltrami operator along the surface of subcortical structures of the brain. The eigenfunctions are then used to construct the heat kernel and used in smoothing out measurements noise along the surface. The proposed framework is applied in investigating the influence of age (38-79 years) and gender on amygdala and hippocampus shape. We detected a significant age effect on hippocampus in accordance with the previous studies. In addition, we also detected a significant gender effect on amygdala. Since we did not find any such differences in the traditional volumetric methods, our results demonstrate the benefit of the current framework over traditional volumetric methods.

[11C]-(R)-PK11195 positron emission tomography in patients with complex regional pain syndrome: A pilot study.

Abstract Complex regional pain syndrome (CRPS) is characterized by severe and chronic pain, but the pathophysiology of this disease are not clearly understood. The primary aim of our case–control study was to explore neuroinflammation in patients with CRPS using positron emission tomography (PET), with an 18-kDa translocator protein specific radioligand [11C]-(R)-PK11195. [11C]-(R)-PK11195 PET scans were acquired for 11 patients with CRPS (30–55 years) and 12 control subjects (30–52 years). Parametric image of distribution volume ratio (DVR) for each participant was generated by applying a relative equilibrium-based graphical analysis. The DVR of [11C]-(R)-PK11195 in the caudate nucleus (t(21) = −3.209, P = 0.004), putamen (t(21) = −2.492, P = 0.022), nucleus accumbens (t(21) = −2.218, P = 0.040), and thalamus (t(21) = −2.395, P = 0.026) were significantly higher in CRPS patients than in healthy controls. Those of globus pallidus (t(21) = −2.045, P = 0.054) tended to be higher in CRPS patients than in healthy controls. In patients with CRPS, there was a positive correlation between the DVR of [11C]-(R)-PK11195 in the caudate nucleus and the pain score, the visual analog scale (r = 0.661, P = 0.026, R2 = 0.408) and affective subscales of McGill Pain Questionnaire (r = 0.604, P = 0.049, R2 = 0.364). We demonstrated that neuroinflammation of CRPS patients in basal ganglia. Our results suggest that microglial pathology can be an important pathophysiology of CRPS. Association between the level of caudate nucleus and pain severity indicated that neuroinflammation in this region might play a key role. These results may be essential for developing effective medical treatments.