Individual parcellation of resting fMRI with a group functional connectivity prior.

Cortical parcellation based on resting fMRI is an important tool for investigating the functional organization and connectivity of the cerebral cortex. Group parcellation based on co-registration of anatomical images to a common atlas will inevitably result in errors in the locations of the boundaries of functional parcels when they are mapped back from the atlas to the individual. This is because areas of functional specialization vary across individuals in a manner that cannot be fully determined from the sulcal and gyral anatomy that is used for mapping between atlas and individual. We describe a method that avoids this problem by refining an initial group parcellation so that for each subject the parcel boundaries are optimized with respect to that subject's resting fMRI. Initialization with a common parcellation results in automatic correspondence between parcels across subjects. Further, by using a group sparsity constraint to model connectivity, we exploit group similarities in connectivity between parcels while optimizing their boundaries for each individual. We applied this approach with initialization on both high and low density group cortical parcellations and used resting fMRI data to refine across a group of individuals. Cross validation studies show improved homogeneity of resting activity within the refined parcels. Comparisons with task-based localizers show consistent reduction of variance of statistical parametric maps within the refined parcels relative to the group-based initialization indicating improved delineation of regions of functional specialization. This method enables a more accurate estimation of individual subject functional areas, facilitating group analysis of functional connectivity, while maintaining consistency across individuals with a standardized topological atlas.

Removal of olefinic fat chemical shift artifact in diffusion MRI.

Diffusion-weighted (DW) MRI has emerged as a key tool for assessing the microstructure of tissues in healthy and diseased states. Because of its rapid acquisition speed and insensitivity to motion, single-shot echo-planar imaging is the most common DW imaging technique. However, the presence of fat signal can severely affect DW-echo planar imaging acquisitions because of the chemical shift artifact. Fat suppression is usually achieved through some form of chemical shift-based fat saturation. Such methods effectively suppress the signal originating from aliphatic fat protons, but fail to suppress the signal from olefinic protons. Olefinic fat signal may result in significant distortions in the DW images, which bias the subsequently estimated diffusion parameters. This article introduces a method for removing olefinic fat signal from DW images, based on an echo time-shifted acquisition. The method is developed and analyzed specifically in the context of single-shot DW-echo-planar imaging, where image phase is generally unreliable. The proposed method is tested with phantom and in vivo datasets, and compared with a standard acquisition to demonstrate its performance.

Robust water/fat separation in the presence of large field inhomogeneities using a graph cut algorithm.

Water/fat separation is a classical problem for in vivo proton MRI. Although many methods have been proposed to address this problem, robust water/fat separation remains a challenge, especially in the presence of large amplitude of static field inhomogeneities. This problem is challenging because of the nonuniqueness of the solution for an isolated voxel. This paper tackles the problem using a statistically motivated formulation that jointly estimates the complete field map and the entire water/fat images. This formulation results in a difficult optimization problem that is solved effectively using a novel graph cut algorithm, based on an iterative process where all voxels are updated simultaneously. The proposed method has good theoretical properties, as well as an efficient implementation. Simulations and in vivo results are shown to highlight the properties of the proposed method and compare it to previous approaches. Twenty-five cardiac datasets acquired on a short, wide-bore scanner with different slice orientations were used to test the proposed method, which produced robust water/fat separation for these challenging datasets. This paper also shows example applications of the proposed method, such as the characterization of intramyocardial fat.

Joint estimation of water/fat images and field inhomogeneity map.

Water/fat separation in the presence of B 0 field inhomogeneity is a problem of considerable practical importance in MRI. This article describes two complementary methods for estimating the water/fat images and the field inhomogeneity map from Dixon-type acquisitions. One is based on variable projection (VARPRO) and the other on linear prediction (LP). The VARPRO method is very robust and can be used in low signal-to-noise ratio conditions because of its ability to achieve the maximum-likelihood solution. The LP method is computationally more efficient, and is shown to perform well under moderate levels of noise and field inhomogeneity. These methods have been extended to handle multicoil acquisitions by jointly solving the estimation problem for all the coils. Both methods are analyzed and compared and results from several experiments are included to demonstrate their performance.

Accelerating Advanced MRI Reconstructions on GPUs.

Computational acceleration on graphics processing units (GPUs) can make advanced magnetic resonance imaging (MRI) reconstruction algorithms attractive in clinical settings, thereby improving the quality of MR images across a broad spectrum of applications. This paper describes the acceleration of such an algorithm on NVIDIA's Quadro FX 5600. The reconstruction of a 3D image with 128(3) voxels achieves up to 180 GFLOPS and requires just over one minute on the Quadro, while reconstruction on a quad-core CPU is twenty-one times slower. Furthermore, relative to the true image, the error exhibited by the advanced reconstruction is only 12%, while conventional reconstruction techniques incur error of 42%.

A network flow method for improved MR field map estimation in the presence of water and fat.

Field map estimation is an important problem in MRI, with applications such as water/fat separation and correction of fast acquisitions. However, it constitutes a nonlinear and severely ill-posed problem requiring regularization. In this paper, we introduce an improved method for regularized field map estimation, based on a statistically motivated formulation, as well as a novel algorithm for the solution of the corresponding optimization problem using a network flow approach. The proposed method provides theoretical guarantees (local optimality with respect to a large move), as well as an efficient implementation. It has been applied to the water/fat separation problem and tested on a number of challenging datasets, showing high-quality results.

Prevalence of bancroftian filariasis in Burdwan district, West Bengal: II. Vector and microfilariae density in colliery and non-colliery areas.

The paper reports the density of Culex quinquefasciatus, infection and infectivity rates, microfilariae(mf)- density and microfilaraemic persons in the colliery and non-colliery areas of Burdwan district, West Bengal. The numbers C. quinquefasciatus were significantly higher in colliery areas, as compared to non-colliery areas. The infection rate and infectivity rates of the vector were found to be higher in colliery areas. The higher vector density in colliery area is one of the major reasons of higher prevalence of filariasis in that area. However, other environmental factors like exposure of the host to the coal might influence the pathogenesis of filariasis in the colliery area.

Prevalence of Bancroftian filariasis in Burdwan District, west Bengal: a comparative study between colliery and non-colliery areas.

The present study reports results of a survey of bancroftian filariasis in Burdwan district West Bengal. 85,974 persons were examined of which 46,221 were inhabitants of the colliery areas of the district and rest 39,753 were from non-Colliery areas, including urban and rural areas of the district. The clinicopositivity, endemicity, microfilaria(mf)-positivity, mf-clinicopositivity, and mf-density were determined. It was found that all these epidemiological and parasitological parameters were significantly higher in the colliery area as compared to non-colliery area. The high vector density in the colliery area may account for such significantly higher prevalence of filariasis in this area. From a differential count of neutrophils, eosinophils and lymphocytes in the mf-positive cases, it was revealed that neutrophil percentage was significantly (P < 0.01) decreased while eosinophils and Lymphocytes increased. The decrease of neutrophils was correlated ((Correlation co-efficient, r = -0.78) with the increase of lymphocytes, indicating an imbalance in the immune-system of the infected persons. The geographical and geological factors resulting in high vector density are considered responsible for the significantly higher rate of bancroftian filariasis in the Colliery area.

Experimental ocular onchocerciasis: local and systemic antibody and cell-mediated immune responses.

Hartley guinea pigs injected subconjunctivally with Onchocerca lienalis (OL) microfilariae (Mf) develop punctate corneal opacities resembling the punctate keratitis of human onchocerciasis. Antibody production and antigen-induced proliferative responses were studied in conjunctival-associated lymphoid tissues (CALT), spleens (SL) and peripheral blood lymphocytes (PBL) from experimentally infected guinea pigs. Cultured single cell suspensions of CALT, SL and PBL were assayed for IgG1, IgG2, IgA and IgE antibody production. IgG1, IgG2, and IgA Onchocerca-specific antibodies were found in culture supernatants of CALT, SL and PBL. When initiated 10 days after a challenge injection of OL, CALT cultures produced antibody levels equal to or less than those produced by the corresponding SL cultures. When initiated 66 days after the last injection of Mf, CALT cultures produced significantly more antibody than the corresponding SL cultures. Blastogenic responses to OL Mf antigen were observed in peripheral and splenic lymphocytes of OL-infected guinea pigs. Animals given subconjunctival injections of Mf followed by treatment with a microfilaricide had greater responses to OL antigen than those given Mf alone, while responses to phytomitogens were similar in drug-treated and non-treated animals. The CALT was locally immunologically responsive against the subconjunctivally injected OL Mf, with the capacity for localized memory responses. The local immunologic responses to conjunctival Onchocerca microfilariae may play a significant role in the immunopathological reactions of ocular onchocerciasis.

Massive follicular lymphoid hyperplasia in experimental allergic conjunctivitis. Local antibody production.

Acute and recurrent allergic conjunctival reactions were induced in guinea pigs by repeated conjunctival applications of fluoresceinyl ovalbumin (FL-OA) for up to 30 months. Early type I conjunctival reactions developed 11 to 25 days after the initial conjunctival exposure to FL-OA. Continuous topical challenges during a six- to 30-month period caused a variety of reactions, including papillary changes and massive hyperplasia of the conjunctival-associated lymphoid tissues. Hyperplasia of lymphoid tissues was induced during a shorter period (two to five months) with a mixture of FL-OA and phorbol ester. Culture fluid from hyperplastic conjunctival lymphoid tissue showed a ratio of IgG1/IgG2 antibody production of up to 15. A low level of recurrence of type I reactivity, after an initial desensitization phenomenon due to a loss of reactive mast cells, correlated with prominent follicular hyperplasia of the conjunctival-associated lymphoid tissue.

Experimental allergic conjunctivitis: production of different isotypes of antibody by conjunctival-associated lymphoid tissue in culture.

Long-term (greater than 2 years) topical, conjunctival application of fluoresceinyl ovalbumin (FL-OA) induced allergic conjunctivitis-like lesions and hyperplasia of conjunctival-associated lymphoid tissue (CALT) in guinea pigs. Single-cell suspensions of CALT and spleen were prepared by collagenase digestion and cultured with or without FL-OA or lipopolysaccharide; the culture supernatants were assayed for IgG, IgA, IgM, and IgE antibody. Absolute values (ng Ab protein/ml) of anti-FL-OA IgG subclasses (IgG1 and IgG2) were measured using purified preparations of IgG1 and IgG2 anti-FL-OA antibody standards in an enzyme-linked immunosorbent assay. Immunohistochemical studies were performed using frozen sectioned CALT tissues as well as cultured single cells. IgG1, IgG2, IgA, IgM, but not IgE, anti-FL-OA antibodies were detected in the culture supernatants of both CALT and spleen. IgG- and IgA-secreting plasma cells were demonstrated in immunoperoxidase-stained CALT and single-cell cultures. The ratio of IgG1 to IgG2 isotypes produced by CALT in vitro was significantly higher than that produced by spleen and also that found in serum. These findings indicated that a site-specific regulation of antibody isotypes may exist within the hyperplastic CALT induced by the long-term topical exposure to FL-OA.

Autoantibody induced by experimental Onchocerca infection. Effect of different routes of administration of microfilariae and of treatment with diethylcarbamazine citrate and ivermectin.

Hartley guinea pigs were injected with microfilariae (Mf) of Onchocerca lienalis as a model for acute inflammatory responses to Mf in human Onchocerca volvulus infection. IgG autoantibody reactive with a 3 M KCl extract of guinea pig cornea was detected by ELISA in the serum of guinea pigs injected with O. lienalis Mf three or more times sub-conjunctivally, or two or more times subcutaneously. Administration of the microfilaricides diethylcarbamazine citrate and ivermectin did not alter the proportion of animals expressing autoantibody or the mean autoantibody titer. The severity of acute corneal inflammatory reactions to Mf was similar in animals with and without circulating autoantibody. Although autoantibody responses did not correlate with acute corneal inflammatory reactions to dead Mf, the ability of Mf to induce formation of an antibody reactive with a component of autologous cornea suggests that autoimmune mechanisms might participate in chronic onchocercal lesions in the cornea, eg, sclerosing keratitis.

Cell-mediated immune response in Indian kala-azar and post-kala-azar dermal leishmaniasis.

Cell-mediated immune (CMI) response in 16 Indian kala-azar (KA) and 12 post-kala-azar dermal leishmaniasis (PKADL) patients was studied in detail by in vitro lymphocyte transformation experiments and by in vivo skin testing. Peripheral blood lymphocytes of active KA patients failed to be stimulated by leishmania antigen. On the other hand, lymphocytes from a majority of the active KA patients could be stimulated by phytohemagglutinin. Active KA patients also failed to show delayed type hypersensitivity reaction to leishmanin, although 72% of them showed delayed type hypersensitivity to a purified protein derivative of tuberculin. Longitudinal studies indicated that antigen-specific CMI response usually appeared in treated KA patients after 12 to 20 weeks of antileishmanial drug therapy, although individual variations were noted. CMI response in PKADL patients was variable as about two-thirds of them showed positive sensitization to leishmania antigen in either in vivo or in vitro tests. Usually, patients with newly acquired PKADL exhibited better CMI response than those with chronic PKADL. However, lymphocytes from all of these patients could be stimulated normally by phytohemagglutinin. Results presented in this study show an impairment of CMI response in active KA which appears to be more specific to leishmania than generalized in nature. Moreover, restoration of specific T-cell responsiveness was aided by antileishmanial drug therapy which resulted in the reduction of antigenic load by parasite destruction and a concomitant decrease in circulating antibody levels, particularly that of the immunoglobulin G class. We suggest that the protection afforded by specific CMI response against Leishmania donovani infection may not be absolute and probably depends on other host-related factors leading to parasite destruction and patient recovery.

Serological profiles in Indian post kala-azar dermal leishmaniasis.

The sera of 20 Indian post kala-azar dermal leishmaniasis (PKADL) patients were analysed for immunoglobulin (IgG, IgM and IgA), third component of complement (C3) and specific antibody contents and the results compared with those of normal controls and kala-azar (KA) patients as obtained in an earlier study. Mean values of serum IgG and IgM in PKADL were found to be significantly higher than those of normal controls, although these values were substantially lower to those of KA patients. No significant difference, however, was noted in the mean levels of serum IgA and C3 between PKADL and control groups. Specific antibodies to Leishmania antigen could be demonstrated in PKADL sera by the indirect haemagglutination (IHA) and enzyme-linked immunosorbent assay (ELISA) methods. Most of these antibodies belonged to IgG class although some IgM antibodies were also demonstrable. Antibody titre ranges in PKADL sera were, however, definitely lower than those of KA sera. A reasonably good correlation between the severity of dermal lesions and IgG-ELISA titres was obtained. Of 12 chronic PKADL cases, only four and ten were found to be serologically positive by IHA and micro-ELISA methods respectively. All eight fresh cases were seropositive by both these tests. Analysis of the data suggests an over-all difference between the serological profiles of PKADL and KA patients.

Serological investigations on Indian kala-azar.

Detailed serological investigations were carried out in forty-nine active kala-azar (KA) cases in North Bihar, India. Various classes of immunoglobulin (IgG, IgA, and IgM) and third component of complement (C3) levels were determined in these sera and results were compared with those obtained in normal controls. Antibody titres were determined by the indirect haemagglutination (IHA) method using soluble Leishmania antigen. Immunoglobulin G and M class-specific antibody titres were also determined separately by the enzyme-linked immunosorbent assay (ELISA) method. Polyclonal hypergammaglobulinaemia with marked increase in serum IgG (and to a lesser extent in IgM) level was a rather common feature in the majority of these sera. Much of this immunoglobulin increase, however, appeared to be non-specific in nature and no absolute correlation could be noted between serum IgG or IgM levels and corresponding IgG or IgM antibody titres. Significant decrease in serum C3 level was observed in KA and this decrease was found to be independent of immunoglobulin levels or specific antibody titres. A fairly good correlation between aldehyde test and serum IgG level was evident from this study. Aldehyde-positive KA sera usually gave higher antibody titres than aldehyde-negative ones. Anti-leishmanial antibodies belonged mostly to IgG class although some IgM antibodies were also demonstrable. The latter class of antibodies probably appeared early in KA infection although their serological specificity was poorer to IgG antibodies. Out of forty-nine KA sera examined in this study thirty-six (73.5%) gave positive IHA titres while forty-six (93.9%) were positive by IgG-ELISA which appeared to be a highly specific and sensitive serodiagnostic method particularly for the early detection of KA cases.