LOCALIZATION OF SPATIALLY EXTENDED BRAIN SOURCES BY FLEXIBLE ALTERNATING PROJECTION (FLEX-AP).

Magnetoencephalography (MEG) and electroencephalography (EEG) are widely employed techniques for the in-vivo measurement of neural activity with exceptional temporal resolution. Modeling the neural sources underlying these signals is of high interest for both neuroscience research and pathology. The method of Alternating Projection (AP) was recently shown to outperform the well-established recursively applied and projected multiple signal classification (RAP-MUSIC) algorithm. In this work, we further enhanced AP to allow for source extent estimation, a novel approach termed flexible extent AP (FLEX-AP). We found that FLEX-AP achieves significantly lower errors for spatially coherent sources compared to AP, RAP-MUSIC, and the corresponding extension, FLEX-RAP-MUSIC. We also found an advantage for discrete dipoles under forward modeling errors encountered in real-world scenarios. Together, our results indicate that the FLEX-AP method can unify dipole fitting and distributed source imaging into a single algorithm with promising accuracy.

An F-ratio-based method for estimating the number of active sources in MEG.

Introduction: Magnetoencephalography (MEG) is a powerful technique for studying the human brain function. However, accurately estimating the number of sources that contribute to the MEG recordings remains a challenging problem due to the low signal-to-noise ratio (SNR), the presence of correlated sources, inaccuracies in head modeling, and variations in individual anatomy. Methods: To address these issues, our study introduces a robust method for accurately estimating the number of active sources in the brain based on the F-ratio statistical approach, which allows for a comparison between a full model with a higher number of sources and a reduced model with fewer sources. Using this approach, we developed a formal statistical procedure that sequentially increases the number of sources in the multiple dipole localization problem until all sources are found. Results: Our results revealed that the selection of thresholds plays a critical role in determining the method's overall performance, and appropriate thresholds needed to be adjusted for the number of sources and SNR levels, while they remained largely invariant to different inter-source correlations, translational modeling inaccuracies, and different cortical anatomies. By identifying optimal thresholds and validating our F-ratio-based method in simulated, real phantom, and human MEG data, we demonstrated the superiority of our F-ratio-based method over existing state-of-the-art statistical approaches, such as the Akaike Information Criterion (AIC) and Minimum Description Length (MDL). Discussion: Overall, when tuned for optimal selection of thresholds, our method offers researchers a precise tool to estimate the true number of active brain sources and accurately model brain function.

Source Aware Deep Learning Framework for Hand Kinematic Reconstruction Using EEG Signal.

The ability to reconstruct the kinematic parameters of hand movement using noninvasive electroencephalography (EEG) is essential for strength and endurance augmentation using exoskeleton/exosuit. For system development, the conventional classification-based brain-computer interface (BCI) controls external devices by providing discrete control signals to the actuator. A continuous kinematic reconstruction from EEG signal is better suited for practical BCI applications. The state-of-the-art multivariable linear regression (mLR) method provides a continuous estimate of hand kinematics, achieving a maximum correlation of up to 0.67 between the measured and the estimated hand trajectory. In this work, three novel source aware deep learning models are proposed for motion trajectory prediction (MTP). In particular, multilayer perceptron (MLP), convolutional neural network-long short-term memory (CNN-LSTM), and wavelet packet decomposition (WPD) for CNN-LSTM are presented. In addition, novelty in the work includes the utilization of brain source localization (BSL) [using standardized low-resolution brain electromagnetic tomography (sLORETA)] for the reliable decoding of motor intention. The information is utilized for channel selection and accurate EEG time segment selection. The performance of the proposed models is compared with the traditionally utilized mLR technique on the reach, grasp, and lift (GAL) dataset. The effectiveness of the proposed framework is established using the Pearson correlation coefficient (PCC) and trajectory analysis. A significant improvement in the correlation coefficient is observed when compared with the state-of-the-art mLR model. Our work bridges the gap between the control and the actuator block, enabling real-time BCI implementation.

Anatomical harmonics basis based brain source localization with application to epilepsy.

Brain Source Localization (BSL) using Electroencephalogram (EEG) has been a useful noninvasive modality for the diagnosis of epileptogenic zones, study of evoked related potentials, and brain disorders. The inverse solution of BSL is limited by high computational cost and localization error. The performance is additionally limited by head shape assumption and the corresponding harmonics basis function. In this work, an anatomical harmonics basis (Spherical Harmonics (SH), and more particularly Head Harmonics (H2)) based BSL is presented. The spatio-temporal four shell head model is formulated in SH and H2 domain. The anatomical harmonics domain formulation leads to dimensionality reduction and increased contribution of source eigenvalues, resulting in decreased computation and increased accuracy respectively. The performance of spatial subspace based Multiple Signal Classification (MUSIC) and Recursively Applied and Projected (RAP)-MUSIC method is compared with the proposed SH and H2 counterparts on simulated data. SH and H2 domain processing effectively resolves the problem of high computational cost without sacrificing the inverse source localization accuracy. The proposed H2 MUSIC was additionally validated for epileptogenic zone localization on clinical EEG data. The proposed framework offers an effective solution to clinicians in automated and time efficient seizure localization.

Adaptive area-preserving parameterization of open and closed anatomical surfaces.

The parameterization of open and closed anatomical surfaces is of fundamental importance in many biomedical applications. Spherical harmonics, a set of basis functions defined on the unit sphere, are widely used for anatomical shape description. However, establishing a one-to-one correspondence between the object surface and the entire unit sphere may induce a large geometric distortion in case the shape of the surface is too different from a perfect sphere. In this work, we propose adaptive area-preserving parameterization methods for simply-connected open and closed surfaces with the target of the parameterization being a spherical cap. Our methods optimize the shape of the parameter domain along with the mapping from the object surface to the parameter domain. The object surface will be globally mapped to an optimal spherical cap region of the unit sphere in an area-preserving manner while also exhibiting low conformal distortion. We further develop a set of spherical harmonics-like basis functions defined over the adaptive spherical cap domain, which we call the adaptive harmonics. Experimental results show that the proposed parameterization methods outperform the existing methods for both open and closed anatomical surfaces in terms of area and angle distortion. Surface description of the object surfaces can be effectively achieved using a novel combination of the adaptive parameterization and the adaptive harmonics. Our work provides a novel way of mapping anatomical surfaces with improved accuracy and greater flexibility. More broadly, the idea of using an adaptive parameter domain allows easy handling of a wide range of biomedical shapes.

CCL2 conditionally determines CCL22-dependent Th2-accumulation during TGF-ß-induced breast cancer progression.

We investigated expressions of -CC chemokine ligand 2 (CCL2) and CCL5 in tumor samples from 147 breast cancer (BCa) patients and correlated with transforming growth factor-ß (TGF-ß) expression. We observed an inverse correlation of TGF-ß expression with CCL2, CCL5 expression in early stages of BCa. On contrary, in late stages, CCL2, not CCL5, expression was found to be directly proportional with TGF-ß expression. TGF-ß stimulated MDA-MB-231 cells to express CCL2, however, downregulated both CCL2 and CCL5 in MCF-7. Interestingly, a significant swing of Th1-Th2 ratio towards Th2 is seen within the primary tumors expressing moderate/high-CCL2-low/negative-CCL5. We observed that CCL2-CCR2 interaction induces monocytes/macrophages to secrete Th2-attracting chemokine CCL22 in vitro. Therefore, CCL2 secreted from the tumor microenvironment may attract and interact with monocytes/macrophages, and favor Th2 accumulation by inducing CCL22 secretion. Study in 4T1-BALB/c BCa mouse model demonstrated significant (p<0.05) decrease in CCL2, CCL5 and CCL22 levels and reduction in lung metastatic nodule numbers upon administering TGF-ß inhibitor. These findings collectively indicate that TGF-ß regulates CCL2 and CCL5 expression in a stage-dependent manner during BCa progression, which in turn, determines Th1-Th2 balance within the tumor microenvironment.

A clinicopathological study of peripheral lymph nodes in HIV-infected patients with special reference to CD4+ T-cell counts: Experience from a tertiary care institution in Darjeeling (India).

BACKGROUND: HIV/AIDS is a major health burden worldwide. India bears the third highest HIV-patients load globally. In the Darjeeling district, HIV-prevalence is >1% with very little known about the profile of HIV-lymphadenopathy. The aim of this study was to identify the different causes of peripheral lymphadenopathy among HIV-infected patients in this region, correlate them with CD4+ T-cell counts and formulate some common clinico-haematological parameters as potential predictors of CD4+ T-cell count. METHODS: In the present study, 76 cases were evaluated. Fine Needle Aspiration Cytology (FNAC) was performed as an out-patient procedure in the Department of Pathology. Smears were stained routinely with Haematoxylin-Eosin and Leishman stains. ZN stains were done when indicated by the cytological findings. Immediate CD4+ T-cell count was obtained by referring the patients to the Anti-retroviral therapy centre. RESULTS: Cytological diagnoses included tuberculosis (82.9%), reactive hyperplasia (6.6%), nonspecific granulomatous lesions (3.9%), non-Hodgkin lymphoma (2.6%), histoplasmosis (2.6%) and simultaneous filariasis with toxoplasmosis (1.3%). Statistically, the opportunistic infections and lymphomas significantly concurred with a CD4+ T-cell count <350/µl. Likewise, the number of enlarged lymph nodes and absolute lymphocyte count (ALC) were found to be useful predictors of CD4+ T-cell counts. CONCLUSIONS: Lymph node cytology in HIV-infected patients is essential to identify opportunistic infections from neoplastic lesions and; to enable therapeutic strategies. Correlation of lesions with mean CD4+ T-cell count predicts personal immunity, stage of disease and disease activity. Furthermore, enlarged lymph node numbers and ALC can be surrogate markers of CD4+ T-cell count for monitoring the severity of the immune suppression in under-resourced countries like India.

Fourier-transform-infrared-spectroscopy based spectral-biomarker selection towards optimum diagnostic differentiation of oral leukoplakia and cancer.

In search of specific label-free biomarkers for differentiation of two oral lesions, namely oral leukoplakia (OLK) and oral squamous-cell carcinoma (OSCC), Fourier-transform infrared (FTIR) spectroscopy was performed on paraffin-embedded tissue sections from 47 human subjects (eight normal (NOM), 16 OLK, and 23 OSCC). Difference between mean spectra (DBMS), Mann-Whitney's U test, and forward feature selection (FFS) techniques were used for optimising spectral-marker selection. Classification of diseases was performed with linear and quadratic support vector machine (SVM) at 10-fold cross-validation, using different combinations of spectral features. It was observed that six features obtained through FFS enabled differentiation of NOM and OSCC tissue (1782, 1713, 1665, 1545, 1409, and 1161 cm(-1)) and were most significant, able to classify OLK and OSCC with 81.3 % sensitivity, 95.7 % specificity, and 89.7 % overall accuracy. The 43 spectral markers extracted through Mann-Whitney's U Test were the least significant when quadratic SVM was used. Considering the high sensitivity and specificity of the FFS technique, extracting only six spectral biomarkers was thus most useful for diagnosis of OLK and OSCC, and to overcome inter and intra-observer variability experienced in diagnostic best-practice histopathological procedure. By considering the biochemical assignment of these six spectral signatures, this work also revealed altered glycogen and keratin content in histological sections which could able to discriminate OLK and OSCC. The method was validated through spectral selection by the DBMS technique. Thus this method has potential for diagnostic cost minimisation for oral lesions by label-free biomarker identification.

Polymerase chain reaction and deoxyribonucleic acid-sequencing based study on distribution of human papillomavirus 16/18 among histopathological types of cervical intra-epithelial neoplasia and primary invasive cervical carcinoma: A scenario in North Bengal, India.

INTRODUCTION: Human papillomavirus (HPV) types 16/18 are reportedly most common in cervical cancer (CaCx) with geographical variation of genotypes. HPV16 predominates both in squamous cell carcinoma (SCC) and adenocarcinoma in India, contrary to reported global predominance of HPV18 in the latter. Our study was aimed to determine the occurrence of HPV16/18 among histopathological types of cervical intra-epithelial neoplasia (CIN) and invasive CaCx from North Bengal, India and to identify any major deviation from the known Indian scenario of distribution of HPV16/18 genotypes in cases of SCC and adenocarcinoma. MATERIALS AND METHODS: This was a retrospective, cross-sectional, case-only type of study, in which 40 cases were histopathologically diagnosed as CIN/CaCx, on which polymerase chain reaction (PCR), deoxyribonucleic acid (DNA)-sequencing and bioinformatics by basic search local alignment tool were performed for HPV-genotyping. STATISTICAL ANALYSIS: The distribution of HPV genotypes among cases of SCC and adenocarcinoma was compared by Fisher's exact-test. RESULTS: HPV was detected in 97.5% (39/40) cases. HPV16-infected cases (32/39; 82.05%) predominated over HPV18-infected ones (7/39; 17.95%). However, HPV18-only infection was significantly (P = 0.0045, one-sided Fisher's exact test) more among adenocarcinoma (3/4; 75%) than SCC (2/26; 7.69%) contrary to HPV16-only infection (SCC = 24/26, 92.31%; adenocarcinoma = 1/4; 25%) whereas both CIN3 cases were HPV16-positive. CONCLUSION: Predominance of HPV18 over HPV16 in cases of adenocarcinoma in this region was contrasting to that of earlier Indian studies suggesting research on HPV18 related cervical carcinogenesis. PCR and DNA-sequencing could prove to be highly effective tools in HPV detection and genotyping. The study reported HPV16/18 infection in almost 98% of the cases, the knowledge about which might prove useful in future population based studies on HPV genotyping and designing of appropriate HPV-vaccines for this region.

Cytohistopathological correlation of a case of squamous cell carcinoma of gallbladder with lymph node metastasis.

Primary carcinomas of the gallbladder are rare malignancies and adenocarcinoma is the more common subtype. Primary squamous cell carcinoma of the gallbladder has rarely been diagnosed by aspiration cytology. Here, we present a case of a 62-year old female patient suffering from abdominal complaints who underwent ultrasound-guided fine-needle aspiration cytology and was diagnosed as keratinizing squamous cell carcinoma of gallbladder. The diagnosis was confirmed on subsequent histopathological examination that also revealed metastasis in the cystic lymph node. Histogenesis and biological behavior of squamous cell carcinoma of gallbladder remains a matter of debate but the role of aspiration cytology in diagnosing these lesions cannot be undermined.

Cytologic diagnosis of undifferentiated high grade pleomorphic sarcoma of breast presenting with brain metastasis.

Primary sarcoma of breast are rare. Diagnosis by aspiration cytology is difficult due to nonspecific cytomorphologic features. An initial presentation with neurological symptoms due to metastasis of breast sarcoma to the brain has not been previously reported. Here, we describe a case of a 60-year-old female who presented with headache, dizziness and convulsion and was subsequently diagnosed with undifferentiated high grade pleomorphic sarcoma of breast with cerebellar metastasis.

Infratentorial medulloepithelioma with divergent differentiation: Possibly a predictor of poor outcome.

Medulloepitheliomas (WHO grade IV) are rare, malignant embryonal tumors of pediatric population, classified under the central nervous system (CNS) primitive neuroectodermal tumors (PNET). Histologically, these tumors are characterized by neoplastic neuroepithelium recapitulating the embryonic neural tube. We describe a rare case of infratentorial medulloepithelioma with divergent differentiation in a 1-year-old male child who presented with headache, vomiting, and seizures. Histopathologic examination of the excised tumor revealed the characteristic neuroepithelium, along with other areas showing primitive neuroectodermal (blastemal) cells in sheets, ependymoblastic rosettes, and nodular areas of neuronal differentiation. Possibly, this proliferating immature neuroepithelium is the cause of poor outcome in medulloepitheliomas. Due to the rarity of these tumors, it remains to be established whether infratentorial location or tumors with divergent differentiation are also predictors of adverse prognosis.

Pediatric hydronephrotic segmental renal dysplasia with ipsilateral ureterovesical obstruction--rare coincidence or a consequence?

Obstruction in the developing urinary tract during embryonic life is one of the factors promoting disordered metanephric development in renal dysplasia. Dysplastic kidneys usually undergo involution during the first 5 years of life. Herein, we narrate a rare case of hydronephrotic segmental dysplasia co-existing with ipsilateral ureterovesical obstruction, in a 7-year-old male child, masquerading as hydronephrosis. Etiopathogenesis of segmental dysplasia presenting at this age is not clearly understood, and could be a consequence of intrauterine obstructive uropathy. Histologic evidence of dysplasia in a hydronephrotic kidney should warrant a close follow-up for pathologic changes in the contralateral kidney or urinary tract.

Radio-pathological diagnosis of hepatobiliary ascariasis: A rare entity.

Ascariasis is the commonest helminthic infection in humans, caused by the nematode Ascaris lumbricoides. The adult worms usually reside in the small intestine. Rarely, they migrate into the bile duct and pancreatic ducts, but involvement of the gall bladder and/or liver parenchyma is extremely rare. Here, we describe a case of a 32-year-old woman who presented with fever, anorexia, right upper quadrant pain and mild hepatomegaly. Ultrasonography revealed a liver abscess and a concurrent moving adult worm in the gall bladder. Fine-needle aspiration cytology (FNAC) from the liver abscess showed presence of fertilized eggs of Ascaris lumbricoides. A diagnosis of gall bladder and hepatic ascariasis was made. The patient responded well to conservative management. Ascaris-induced liver abscess with concurrent living adult worm in gall bladder has rarely been reported. Ultrasonography and FNAC are important diagnostic modalities for detection of such lesions. Conservative management appears to be the treatment of choice for hepatobiliary ascariasis.

An unusual case of thyroid papillary carcinoma with solitary cerebral metastasis presenting with neurological symptoms.

Papillary carcinoma of the thyroid is well known for metastasis to regional lymph nodes resulting in early detection and overall favorable prognosis. Solitary metastasis of papillary carcinoma of the thyroid in the cerebrum is extremely rare with only a few cases reported in the literature. Here, we report an unusual case of a 40-year-old female patient who presented with neurological symptoms and a radiological diagnosis of meningioma was made. Subsequent histopathology from the resected brain tumor revealed a solitary cerebral metastasis from papillary carcinoma of the thyroid. There was no involvement of regional lymph nodes and the radiological findings were indicative of a primary brain tumor.

Dermatofibrosarcoma protuberans of the scalp: a relatively unusual site of occurrence.

Dermatofibrosarcoma protruberans is an uncommon low grade soft tissue tumor comprising of only 5% of adult soft tissue sarcomas. Scalp is a relatively uncommon site of occurrence for this tumor. Its identification at this site and differentiation from benign fibrous histiocytoma is important due to the propensity of recurrence and metastasis in the former unless a wide, optimal surgical margin is ensured during excision.

Computed tomography guided fine needle aspiration cytology of mass lesions of lung: Our experience.

CONTEXT: Computerized tomography (CT) guided fine needle aspiration cytology (FNAC) of lung lesions has rapidly emerged as a less-invasive, cheap, rapid and fairly accurate diagnostic aid in lung lesions. AIMS: The purpose of this present study was to evaluate the effectiveness of CT-guided FNAC in the diagnosis of pulmonary mass lesions (both benign and malignant) and to determine the complication rate of this procedure. SETTINGS AND DESIGN: We conducted an institution-based, prospective study on 127 patients who presented with pulmonary mass lesions. MATERIALS AND METHODS: After proper consent was obtained, CT-guided transthoracic fine needle aspiration was done and their diagnoses were confirmed by appropriate methods. The results were analyzed statistically. RESULTS: Out of 127 cases selected for the study, 59.8% were males while the rest were females. Cough was the most common symptom present in 71.2% cases, followed by weight loss (62.4%). 21.2% cases were cytologically benign. Adenocarcinoma (54.2%) was the commonest malignant tumor. FNAC provided at least 96% sensitivity and 100% specificity in diagnosing lung tumors. Among the benign lesions, specific diagnoses were obtained in 48.1% cases. Thus, altogether a specific diagnosis was obtained in 109 of 127 cases, i.e. 85.8%. No major complication was noted. CONCLUSIONS: CT-guided FNAC is an extremely valuable and fairly accurate diagnostic aid of intrathoracic mass lesions, with a reasonable rate of complication.

Sarcomatoid chromophobe renal cell carcinoma: Cytohistopathological correlation of a case.

Sarcomatoid renal cell carcinomas of the kidney are rare neoplasms constituting about 1-5% of all renal malignant neoplasms. These are aggressive tumors and are commonly associated with conventional (clear cell) renal cell carcinomas, but cases associated with chromophobe renal cell carcinomas are sparse. Cytological features of such lesions have rarely been reported. Here, we report a unique case of a 48-year-old male patient who presented with right flank lump and pain. A fine needle aspiration was performed from the lesion under ultrasound guidance and a cytological diagnosis of pleomorphic sarcoma was made. A right-sided radical nephrectomy was carried out and subsequent histopathology revealed a sarcomatoid renal cell carcinoma with wide areas of necrosis coexisting with chromophobe renal cell carcinoma with calcification. Differentiation of pleomorphic sarcoma from a sarcomatoid renal cell carcinoma is, thus, challenging from cytopathology smears and the differential diagnoses should always be borne in mind while giving a cytopathological opinion.

Fine needle aspiration biopsy in the diagnosis of intraocular and extra-ocular mass lesions.

In a 3-year study with mass lesions related to ophthalmology 30 cases arising from ocular tissue, ocular adenaxae and orbit were subjected to fine needle aspiration biopsy. Of these 27 cases were further subjected to detailed histopathological examination. Fine needle aspiration biopsy revealed definitive cytological character in 23 cases consistent with histopathological and clinical diagnosis.

Idiopathic granulomatous mastitis-utility of fine needle aspiration cytology (FNAC) in preventing unnecessary surgery.

OBJECTIVE: Granulomatous mastitis is a benign disorder which closely mimics malignancy clinico-radiologically. A simple and cost effective modality like fine needle aspiration cytology (FNAC) can help in prompt diagnosis and avoid unnecessary surgery. MATERIAL AND METHODS: A retrospective study where data were collected for granulomatous lesions of the breast diagnosed by histopathology in a five year period and review of FNAC slides. Cases positive for Mycobacterium tuberculosis either on ZN stain or Polymerase chain reaction (PCR) and fungus were excluded. A total of 8 cases were included in our study for analysis. RESULTS: All the cases showed the presence of granuloma composed of epithelioid histiocytes against a background of giant cells, polymorphs with absence of necrosis. CONCLUSION: Cytological diagnosis of granulomatous mastitis is difficult as it overlaps with other etiologies like tuberculosis which is prevalent in this part of the world. However, with the use of ancillary techniques like PCR and negative microbiological investigations, a definitive diagnosis can be made.