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Inhibitors of kinases involved in signaling and other intracellular pathways, have revolutionized cancer treatment by providing highly targeted and effective therapies. However, timely monitoring treatment response remains a considerable challenge since conventional methods such as assessing changes in tumor volume do not adequately capture early responses or resistance development, due to the predominantly cytostatic rather than cytotoxic effect of kinase inhibitors. Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that can provide insights into cellular metabolism by detecting changes in metabolite concentrations. By measuring metabolite levels, MRS offers a means to assess treatment response in real-time, providing earlier indications of efficacy or resistance compared to conventional imaging modalities. Bruton's Tyrosine Kinase (BTK) is a critical enzyme involved in B-cell receptor signaling. BTK inhibitors have been approved for the treatment of Mantle Cell Lymphoma (MCL) and other B-cell malignancies. Recent studies involving genome-scale gene expression, metabolomic, and fluxomic analyses have demonstrated that ibrutinib, an index BTK inhibitor, profoundly affects the key metabolic pathways in MCL cells., including glycolysis, glutaminolysis, pentose shunt, TCA cycle and phospholipid metabolism. Importantly, the effects of ibrutinib on MCL cells directly and proportionately correlates with their sensitivity to the drug. Consequently, changes in specific metabolite concentrations detectable non-invasively by MRS such as lactate and alanine reflecting mostly the status of cellular glycolysis and glutaminolysis, respectively, have emerged as potential biomarkers for predicting response and resistance of MCL cells to BTK inhibition, both in vitro and in vivo. Preparations to validate the utility of these biomarkers in clinical setting are under way. These studies may pave the way to monitor therapeutic response to kinase inhibitors also in other types of cancer.
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BACKGROUND: Inhibition of kinases is the ever-expanding therapeutic approach to various types of cancer. Typically, assessment of the treatment response is accomplished by standard, volumetric imaging procedures, performed weeks to months after the onset of treatment, given the predominantly cytostatic nature of the kinase inhibitors, at least when used as single agents. Therefore, there is a great clinical need to develop new monitoring approaches to detect the response to kinase inhibition much more promptly. Noninvasive 1H magnetic resonance spectroscopy (MRS) can measure in vitro and in vivo concentration of key metabolites which may potentially serve as biomarkers of response to kinase inhibition. METHODS: We employed mantle cell lymphoma (MCL) cell lines demonstrating markedly diverse sensitivity of inhibition of Bruton's tyrosine kinase (BTK) regarding their growth and studied in-depth effects of the inhibition on various aspects of cell metabolism including metabolite synthesis using metabolomics, glucose and oxidative metabolism by Seahorse XF technology, and concentration of index metabolites lactate, alanine, total choline and taurine by 1H MRS. RESULTS: Effective BTK inhibition profoundly suppressed key cell metabolic pathways, foremost pyrimidine and purine synthesis, the citrate (TCA) cycle, glycolysis, and pyruvate and glutamine/alanine metabolism. It also inhibited glycolysis and amino acid-related oxidative metabolism. Finally, it profoundly and quickly decreased concentration of lactate (a product of mainly glycolysis) and alanine (an indicator of amino acid metabolism) and, less universally total choline both in vitro and in vivo, in the MCL xenotransplant model. The decrease correlated directly with the degree of inhibition of lymphoma cell expansion and tumor growth. CONCLUSIONS: Our results indicate that BTK inhibition exerts a broad and profound suppressive effect on cell metabolism and that the affected index metabolites such as lactate, alanine may serve as early, sensitive, and reliable biomarkers of inhibition in lymphoma patients detectable by noninvasive MRS-based imaging method. This kind of imaging-based detection may also be applicable to other kinase inhibitors, as well as diverse lymphoid and non-lymphoid malignancies.
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Agammaglobulinemia Tirosina Quinasa , Linfoma de Células del Manto , Inhibidores de Proteínas Quinasas , Humanos , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/farmacología , Animales , Agammaglobulinemia Tirosina Quinasa/metabolismo , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Linfoma de Células del Manto/metabolismo , Linfoma de Células del Manto/patología , Linfoma de Células del Manto/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones , Biomarcadores/metabolismoRESUMEN
There are a few existing gaps and paucity of literature from Southeast Asia on the prevalence of intestinal parasitic infections among migrant construction workers. The present cross-sectional study was conducted to address this gap among migrant construction workers and their households in Bhopal. The study design included an interview questionnaire survey prior to the enrollment of participants and stool sample collection. The stool samples were processed according to the study protocol of macroscopy, occult blood testing, microscopy techniques combined with modified acid-fast, and sedimentation techniques. Participants were deemed positive if they exhibited microscopic findings in one out of three stool samples per recruit. We recommended clinical consultation for these cases and provided a report. Direct therapeutic intervention was not part of the study. The total recruits were 361. The predominant age group was young, i.e., aged 21 to 30 years (122/361, 33.8%), with the majority of females (55.2%). Most workers were occupied with work of digging soil (47.4%). The majority of participants (93.1%) practiced open field defecation (OFD). The prevalence of intestinal parasitic infections among migrant workers and households was 36.9% (133/361). Monoinfection was 88.7%, with 41% from Entamoeba histolytica/Entamoeba dispar. Monoinfection with Hymenolepis nana (10.2%) was a predominant helminth. The most common coinfection observed was of Giardia intestinalis with Ancylostoma duodenale (26.7%). Hand washing was the only independent predictor with an odds ratio of 3.6. Migrant behavior of the construction workers and their households was the major reason for not reaching the benefits of deworming schemes for children and vulnerability to intestinal parasitic infections.
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Though literacy levels are slowly improving in India due to the steps taken by the Government of India, it has been a challenge for female students with gender disparities in literacy levels. Stress levels are high in students, more so during their exam times. While prior literature has demonstrated the prevalence of stress during student life, there is limited evidence of any interventions to decrease stress and improve satisfaction with life, specifically for female students. Heartfulness meditation is a heart-based meditation practice that may reduce stress and improve satisfaction with life among female students. We conducted a prospective cohort analysis comparing perceived stress and satisfaction with life outcomes among female students who self-selected to participate in the Heartfulness meditation program. The first group, G20, underwent intervention from week 0 until week 12 and continued their practice independently until week 20. The second group, G14, joined the intervention from week 7 until week 12 with only a 6-week exposure to guided meditation sessions through Heartfulness Trainers. They continued their practice independently until week 20. Data on Perceived Stress (PSS) and Satisfaction with Life (SWLS) were collected at week 0 and week 20 for both groups. G20 had 127 participants, and G14 had 113 participants. Ninety-four participants from the G20 group and 93 from G14 completed the study. The G20 group showed a statistically significant reduction of PSS scores from 20.79 to 18.96, and an increase in the SWLS scores from 22.03 to 23.51 from baseline to the end of the study period. The study of the Pearson correlation coefficient indicated that there is a weak positive correlation between pre- and post-scores for both the groups for both PSS and SWLS. Our findings suggest that Heartfulness meditation practice offers significant benefits with perceived stress and satisfaction with life among female students independent of their age. Still, a prolonged guided intervention of over 6 weeks is needed. A larger, randomized study with an additional control group with no meditation intervention is recommended. Clinical trial registration: ISRCTN11302156, https://doi.org/10.1186/ISRCTN11302156.
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Background: Accounting professionals experience a stressful working environment with previous studies demonstrating a high prevalence of burnout. Meditation-based interventions have a potential role in decreasing burnout and improving satisfaction with life. However, the benefits of Heartfulness meditation intervention have not been demonstrated among accounting professionals. Objective: To evaluate the effects of an 8-week Heartfulness Meditation program on burnout and satisfaction with life in chartered accountants. Methods: The study was a prospective cohort analysis comparing burnout and satisfaction with life outcomes among accounting professionals who either self-selected to participate in the Heartfulness Meditation Program (intervention group) or with no particular intervention (control group). Maslach Burnout Inventory (MBI) and Satisfaction with Life Scale (SWLS) scores were collected at baseline and at the end of the study period. Results: Two hundred and six participants completed the study. Participants in the intervention group (n = 107) experienced statistically significant improvement in MBI emotional exhaustion from 2.17 to 1.75 (P = .00) and overall MBI score decreased from 2.99 to 2.83 (P = .020). Participants in the control group (n = 99) experienced statistically significant improvement for emotional exhaustion only, from 1.82 to 1.52 (P = .009). Further, participants in the intervention group demonstrated statistically significant improvement with SWLS from 4.90 to 5.17 (P = .005). While participants in the intervention group experienced higher levels of decline (19.55%) compared to the control group (16.41%) for emotional exhaustion, it was not statistically significant. Conclusion: The current study is one of the first attempts of a Heartfulness meditation intervention to reduce burnout and improve satisfaction with life among accounting professionals. Both the intervention group and the control group showed an improvement of emotional exhaustion. The statistically significant improvements observed in the overall MBI and SWLS outcomes in the intervention group suggest an online Heartfulness meditation program could serve as a potential tool for reducing burnout and improving satisfaction among accounting professionals.
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Introduction The proximal femoral nail (PFN) is a widely accepted fixation method for the management of unstable intertrochanteric fractures. Reconstructing the lateral trochanteric wall and ensuring the stability of the trochanteric fragments are considered to be essential for enhancing the prognosis of unstable intertrochanteric fractures. The aim of this study is to evaluate and compare the results of the management of unstable intertrochanteric fracture of the femur using PFN and the screw-augmented PFN (aPFN). Methods This prospective comparative study was undertaken from January 2020 to July 2021 and included 60 patients presenting with unstable intertrochanteric fractures (AO/OTA type 31-A2.2 and 31-A2.3) at a tertiary care teaching institute in northern India. The enrolled patients were randomly divided into two groups (group 1 and group 2) and were managed with screw-augmented PFN and PFN, respectively. Functional outcome was evaluated using the Salvati and Wilson score at the 12-month follow-up. SPSS version 24.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. A p-value less than 0.05 was regarded as significant. Results The average time to union of the fractures in group 1 was 12.66 ± 1.68 weeks, while it was 13.47 ± 1.47 weeks in group 2 (p = 0.055). At the 12-month follow-up, the average functional outcome, as evaluated by Salvati and Wilson score, was 34 ± 2.40 in group 1, whereas it was 31.58 ± 4.4 in group 2; and the difference was observed to be statistically significant (p = 0.011). Group 1 had 28 patients (93.33%) with excellent to good results, while group 2 had 25 patients (83.33%) with excellent to good results. One patient in group 1 and five patients in group 2 had poor outcomes at the 12-month follow-up. Conclusion Screw-augmented PFN has better functional outcomes as compared to PFN alone for the management of unstable intertrochanteric fractures. Hence, in our opinion, screw augmentation of PFN may be the better fixation technique for most unstable intertrochanteric femur fractures.
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Importance of the redox status of nicotinamide adenine dinucleotide (NAD), including its oxidized (NAD+) and reduced (NADH) forms, has been shown in many biological processes. However, NAD(H) redox status assessment is traditionally limited to biochemical assays in vitro or optical redox imaging (ORI) for superficial tissues in vivo and for deep tissues ex vivo. In recent years, phosphorous-31 magnetic resonance spectroscopy (31P-MRS) was utilized to quantify NAD+, NADH, and the redox ratio NAD+/NADH in normal tissues in vivo. The quantification is based on the spectral fitting of the upfield shoulder of the αATP peak that contains signals of NAD+ (a quartet) and NADH (a singlet), assuming pH-independence of peak positions. To evaluate the feasibility of measuring tumour NAD(H) redox status in vivo, we fitted single voxel 31P-MR spectra of subcutaneous mouse xenografts of human breast cancer cell lines acquired on a 9.4-T horizontal bore preclinical MR scanner. We found larger variations in the chemical shift offsets of NAD+ and NADH from αATP in these tumours than the literature values of normal tissues. Furthermore, our 31P-MR spectra of αATP, NAD+, and NADH solution phantoms indicated that the chemical shift of αATP and thus the offsets between NAD(H) and αATP were pH dependent. Therefore, whether tumour pH should be incorporated into the spectral fitting model should be further evaluated. Additionally, spectral resolution and signal-to-noise ratio should be improved by optimising 31P-MRS protocols, increasing data acquisition time, and using a more sensitive coil for signal detection.
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NAD , Neoplasias , Animales , Humanos , Ratones , NAD/metabolismo , Fósforo , Estudios de Factibilidad , Espectroscopía de Resonancia Magnética/métodos , Oxidación-Reducción , Neoplasias/diagnóstico por imagenRESUMEN
As a phosphorus-containing molecule, nicotinamide adenine dinucleotide is visible by phosphorus magnetic resonance spectroscopy (31P-MRS). However, the relatively low cellular levels of its oxidised (NAD+) and reduced (NADH) forms and a significant peak overlap hinder their evaluation in live tissues. This problem is critical when using 31P-MR spectroscopic imaging, where signals are localised from limited tissue volumes. We have reported improvements in spectral resolution of 31P-MRSI of human tissues in situ using a strict optimisation of the static magnetic field (B0 shimming) and 1H-irradiation during 31P acquisition. Given this, we aimed to demonstrate if these improvements allowed us to measure the in vivo intracellular levels of NAD+ and NADH at the relatively low magnetic field of 1.5 tesla (T). Our results show the feasibility of the in vivo determination of NAD+ and NADH from relatively small volumes of human tissues studied at 1.5 T. These results are clinically relevant as the currently available systems for human use mainly operate at 1.5 or 3.0.
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NAD , Fósforo , Humanos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodosRESUMEN
We report a mode-locking operation using a nonlinear multimode interference (MMI)-based saturable absorber in an ytterbium-doped fiber laser under an all-normal dispersion configuration. The MMI is observed in a step-index single mode-multimode-single mode (SMS) fiber structure. The intensity and wavelength-dependent transmission of the SMS structure has been studied numerically to understand the Kerr-induced saturable absorber properties of MMI in a step-index fiber. Numerical investigations show that presence of a narrow-band wavelength-tunable spectral filter is necessary for a nonlinear MMI-based saturable absorber to be effective for mode locking. A single-pulse mode-locking operation in the laser is realized at a very low pump power of ${\sim}{56.3}\;{\rm mW}$ at which the laser generates 180 ps duration pulses at ${\sim}{9}\;{\rm MHz}$ repetition rate with measured signal-to-noise ratio of ${\sim}{50}\;{\rm dB}$. This all-fiber integrated laser operates in multi-pulse and noise-like rectangular pulse regimes at increased pump power.
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Glioblastoma (GBM) is the most malignant brain tumor in adults, with a dismal prognosis despite aggressive multi-modal therapy. Immunotherapy is currently being evaluated as an alternate treatment modality for recurrent GBMs in clinical trials. These immunotherapeutic approaches harness the patient's immune response to fight and eliminate tumor cells. Standard MR imaging is not adequate for response assessment to immunotherapy in GBM patients even after using refined response assessment criteria secondary to amplified immune response. Thus, there is an urgent need for the development of effective and alternative neuroimaging techniques for accurate response assessment. To this end, some groups have reported the potential of diffusion and perfusion MR imaging and amino acid-based positron emission tomography techniques in evaluating treatment response to different immunotherapeutic regimens in GBMs. The main goal of these techniques is to provide definitive metrics of treatment response at earlier time points for making informed decisions on future therapeutic interventions. This review provides an overview of available immunotherapeutic approaches used to treat GBMs. It discusses the limitations of conventional imaging and potential utilities of physiologic imaging techniques in the response assessment to immunotherapies. It also describes challenges associated with these imaging methods and potential solutions to avoid them.
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Neoplasias Encefálicas/diagnóstico por imagen , Diagnóstico por Imagen , Glioblastoma/diagnóstico por imagen , Animales , Neoplasias Encefálicas/etiología , Neoplasias Encefálicas/terapia , Toma de Decisiones Clínicas , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Diagnóstico por Imagen/métodos , Diagnóstico por Imagen/normas , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Glioblastoma/etiología , Glioblastoma/terapia , Humanos , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Pronóstico , Resultado del TratamientoRESUMEN
PURPOSE: It has been reported that diffusion-weighted imaging (DWI) with ultrahigh b-value increases the diagnostic power of prostate cancer. DWI with higher b-value increases the diagnostic power of prostate cancer. DWI with higher b-value increases the diagnostic power of prostate cancer. DWI with higher b-value increases the diagnostic power of prostate cancer. DWI with higher Materials and Methods. Fifteen patients (7 malignant and 8 benign) were included in this study retrospectively with the institutional ethical committee approval. All images were acquired at a 3T MR scanner. The ADC values were calculated using a monoexponential model. Synthetic ADC (sADC) for higher b-value increases the diagnostic power of prostate cancer. DWI with higher. RESULTS: No significant difference was observed between actual ADC and sADC for b-value increases the diagnostic power of prostate cancer. DWI with higher p=0.002, paired t-test) in sDWI as compared to DWI. Malignant lesions showed significantly lower sADC as compared to benign lesions (p=0.002, paired t-test) in sDWI as compared to DWI. Malignant lesions showed significantly lower sADC as compared to benign lesions (Discussion/. CONCLUSION: Our initial investigation suggests that the ADC values corresponding to higher b-value can be computed using log-linear relationship derived from lower b-values (b ≤ 1000). Our method might help clinicians to decide the optimal b-value for prostate lesion identification.b-value increases the diagnostic power of prostate cancer. DWI with higher b-value increases the diagnostic power of prostate cancer. DWI with higher b-value increases the diagnostic power of prostate cancer. DWI with higher b-value increases the diagnostic power of prostate cancer. DWI with higher.
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We report an all-fiber, all-normal dispersion ytterbium (Yb)-doped fiber oscillator mode locked by nonlinear polarization evolution. The mode locking is realized in different pump power regimes by adjusting the polarization controllers. The average output power, pulse energy, and compressed pulse duration varies from 60 to 150 mW, 1.4 to 3.5 nJ, and 350 to 146 fs, respectively, when the pump power to the oscillator is varied from 250 to 500 mW. Particularly at 500 mW pump power, the oscillator generates highly chirped 5 ps duration pulses at 42 MHz that are compressed to a 146 fs duration with a clean temporal profile. The signal-to-noise ratio of the train of mode-locked pulses is 85 dB, indicating stable mode-locking operation. The generalized nonlinear Schrödinger equation is solved numerically to model the passive mode locking in a Yb oscillator, supporting the experimental results. In a chirped pulse Yb amplifier, the signal power is scaled to a 10 W level, and the amplified pulse is compressed to 355 fs duration.
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Delayed brain development in perinatally HIV-infected children may affect the functional brain activity and subsequently cognitive function. The current study evaluated the functional brain activity in HIV-infected children by quantifying the amplitude of low frequency fluctuations (ALFF) and functional connectivity (FC). Additionally, correlation of ALFF and FC with cognitive measures was performed. Twenty-six HIV-infected children and 20 control children underwent neuropsychological (NP) assessment and resting-state functional magnetic resonance imaging (rs-fMRI). ALFF and FC maps were generated and group differences were analyzed using two-sample t-test. Furthermore, ALFF and FC showing significant group differences were correlated with NP scores using Pearson's correlation. Significantly lower ALFF in the left middle temporal gyrus, precentral and post central gyrus was observed in HIV-infected children compared to controls. FC was significantly reduced in the right inferior parietal, vermis, middle temporal and left postcentral regions, and significantly increased in the right precuneus, superior parietal and left middle frontal regions in HIV-infected children as compared to control. HIV-infected children showed significantly lower NP scores in various domains including closure, exclusion, memory, verbal meaning, quantity and hidden figure than controls. These waning cognitive functions were significantly associated with changes in ALFF and FC in HIV-infected children. The findings suggest that abnormal ALFF and FC may responsible for cognitive deficits in HIV-infected children. ALFF and FC in association with cognitive evaluation may provide a clinical biomarker to evaluate functional brain activity and to plan neurocognitive intervention in HIV-infected children undergoing standard treatment.
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Encéfalo/fisiopatología , Encéfalo/virología , Trastornos del Conocimiento/virología , Cognición/fisiología , VIH/patogenicidad , Encéfalo/patología , Mapeo Encefálico/métodos , Niño , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Glioma grade along with patient's age and general health are used for treatment planning and prognosis. PURPOSE: To characterize and quantify the spontaneous blood oxygen level-dependent (BOLD) fluctuations in gliomas using measures based on T2*-weighted signal time-series and to distinguish between high- and low-grade gliomas. STUDY TYPE: Retrospective. SUBJECTS: Twenty-one patients with high-grade and 13 patients with low-grade gliomas confirmed on histology were investigated. FIELD STRENGTH/SEQUENCE: Dynamic T2*-weighted (multislice single-shot echo-planar-imaging) magnetic resonance imaging (MRI) was performed on a 3T system with an 8-element receive-only head coil to measure the BOLD fluctuations. In addition, a dynamic T1 -weighted (3D fast field echo) dynamic contrast-enhanced (DCE) perfusion scan was performed. ASSESSMENT: Three BOLD measures were determined: the temporal shift (TS), amplitude of low frequency fluctuations (ALFF), and regional homogeneity (ReHo). DCE perfusion-based cerebral blood volume (CBV) and time-to-peak (TTP) maps were concurrently evaluated for comparison. STATISTICAL TESTS: An analysis-of-variance test was first used. When the test appeared significant, post-hoc analysis was performed using analysis-of-covariance with age as covariate. Logistic regression and receiver-operator characteristic curve analysis were also performed. RESULTS: TS was significantly advanced in high-grade gliomas compared to the contralateral cortex (P = 0.01) and low-grade gliomas (P = 0.009). In high-grade gliomas, ALFF and CBV were significantly higher than the contralateral cortex (P = 0.041 and P = 0.008, respectively) and low-grade gliomas (P = 0.036 and P = 0.01, respectively). ReHo and TTP did not show significant differences between high- and low-grade gliomas (P = 0.46 and P = 0.42, respectively). The area-under-curve was above 0.7 only for the TS, ALFF, and CBV measures. DATA CONCLUSION: Advanced and amplified hemodynamic fluctuations manifest in high-grade gliomas, but not in low-grade gliomas, and can be assessed using BOLD measures. Preliminary results showed that quantification of spontaneous fluctuations has potential for hemodynamic characterization of gliomas and distinguishing between high- and low-grade gliomas. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018;47:1616-1625.
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Neoplasias Encefálicas/diagnóstico por imagen , Imagen Eco-Planar , Glioma/diagnóstico por imagen , Imagen por Resonancia Magnética , Adolescente , Adulto , Anciano , Circulación Cerebrovascular , Medios de Contraste/química , Reacciones Falso Positivas , Femenino , Hemodinámica , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Perfusión , Pronóstico , Curva ROC , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: Aim of this retrospective study was to compare diagnostic accuracy of proposed automatic normalization method to quantify the relative cerebral blood volume (rCBV) with existing contra-lateral region of interest (ROI) based CBV normalization method for glioma grading using T1-weighted dynamic contrast enhanced MRI (DCE-MRI). MATERIAL AND METHODS: Sixty patients with histologically confirmed gliomas were included in this study retrospectively. CBV maps were generated using T1-weighted DCE-MRI and are normalized by contralateral ROI based method (rCBV_contra), unaffected white matter (rCBV_WM) and unaffected gray matter (rCBV_GM), the latter two of these were generated automatically. An expert radiologist with >10years of experience in DCE-MRI and a non-expert with one year experience were used independently to measure rCBVs. Cutoff values for glioma grading were decided from ROC analysis. Agreement of histology with rCBV_WM, rCBV_GM and rCBV_contra respectively was studied using Kappa statistics and intra-class correlation coefficient (ICC). RESULT: The diagnostic accuracy of glioma grading using the measured rCBV_contra by expert radiologist was found to be high (sensitivity=1.00, specificity=0.96, p<0.001) compared to the non-expert user (sensitivity=0.65, specificity=0.78, p<0.001). On the other hand, both the expert and non-expert user showed similar diagnostic accuracy for automatic rCBV_WM (sensitivity=0.89, specificity=0.87, p=0.001) and rCBV_GM (sensitivity=0.81, specificity=0.78, p=0.001) measures. Further, it was also observed that, contralateral based method by expert user showed highest agreement with histological grading of tumor (kappa=0.96, agreement 98.33%, p<0.001), however; automatic normalization method showed same percentage of agreement for both expert and non-expert user. rCBV_WM showed an agreement of 88.33% (kappa=0.76,p<0.001) with histopathological grading. CONCLUSION: It was inferred from this study that, in the absence of expert user, automated normalization of CBV using the proposed method could provide better diagnostic accuracy compared to the manual contralateral based approach.
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Neoplasias Encefálicas/diagnóstico , Glioma/diagnóstico , Imagen por Resonancia Magnética , Neoplasias Encefálicas/patología , Circulación Cerebrovascular , Medios de Contraste/química , Estudios Transversales , Diagnóstico por Computador , Glioma/patología , Sustancia Gris/patología , Humanos , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reconocimiento de Normas Patrones Automatizadas , Curva ROC , Radiólogos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Sustancia Blanca/patologíaRESUMEN
Pediatric HIV patients often suffer with neurodevelopmental delay and subsequently cognitive impairment. While tissue injury in cortical and subcortical regions in the brain of adult HIV patients has been well reported there is sparse knowledge about these changes in perinatally HIV infected pediatric patients. We analyzed cortical thickness, subcortical volume, structural connectivity, and neurocognitive functions in pediatric HIV patients and compared with those of pediatric healthy controls. With informed consent, 34 perinatally infected pediatric HIV patients and 32 age and gender matched pediatric healthy controls underwent neurocognitive assessment and brain magnetic resonance imaging (MRI) on a 3 T clinical scanner. Altered cortical thickness, subcortical volumes, and abnormal neuropsychological test scores were observed in pediatric HIV patients. The structural network connectivity analysis depicted lower connection strengths, lower clustering coefficients, and higher path length in pediatric HIV patients than healthy controls. The network betweenness and network hubs in cortico-limbic regions were distorted in pediatric HIV patients. The findings suggest that altered cortical and subcortical structures and regional brain connectivity in pediatric HIV patients may contribute to deficits in their neurocognitive functions. Further, longitudinal studies are required for better understanding of the effect of HIV pathogenesis on brain structural changes throughout the brain development process under standard ART treatment.
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Mapeo Encefálico , Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/diagnóstico por imagen , Trastornos del Conocimiento/etiología , Infecciones por VIH/complicaciones , Adolescente , Antígenos CD4/metabolismo , Niño , Femenino , Infecciones por VIH/metabolismo , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Vías Nerviosas/diagnóstico por imagen , Pruebas NeuropsicológicasRESUMEN
We report, for what we believe is the first time, generation of stable chair-like pulses (a pulse shape with an initial long flat portion followed by a short high peak power portion resembling the shape of a chair) by mode locking of a Ytterbium (Yb)-doped fiber laser. Chair-like pulse shapes are achieved by implementing dual saturable absorbers, one based on a nonlinear optical loop mirror (NOLM) and the other based on nonlinear polarization rotation (NPR) inside the cavity. The transmission characteristics of the NOLM-NPR pair leading to the formation of chair-like pulses are numerically investigated. We also report the amplification characteristics of chair-like pulses in an external multistage Yb-doped fiber amplifier setup at different repetition rates of the pulse train. It was found that the chair-like pulses are suitable for amplification, and more than 10 W of average power at 460 kHz repetition rate have been obtained at total pump power of â¼20 W coupled to the power amplifier. At a lower repetition rate (115 kHz), â¼8 W of average power were obtained corresponding to â¼70 µJ of pulse energy with negligible contribution from amplified spontaneous emission or stimulated Raman scattering. We believe that such an oscillator-amplifier system could serve as an attractive tool for micromachining applications.
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PURPOSE: Dynamic contrast enhanced (DCE) MRI is used to grade and to monitor the progression of glioma while on treatment. Usually, a fixed hematocrit (Hct) value for adults is assumed to be ~45%; however, it is actually known for individual variations. Purpose of this study was to investigate the effect of measured Hct values in glioma grading using DCE-MRI. MATERIALS AND METHODS: Fifty glioma patients were included in this study. Kinetic and hemodynamic parameters were estimated for each patient using assumed as well as measured Hct values. To look the changes in Hct value over time, Hct was measured multiple times from 10 of these glioma patients who were on treatment. Simulation was done to look for the effect of extreme variations of Hct values on perfusion metrics. The data was compared to look for significant differences in the perfusion metrics derived from assumed and measured Hct values. RESULTS: The measured Hct value in patients was found to be (40.4±4.28)%. The sensitivity and specificity of DCE-MRI parameters in glioma grading were not significantly influenced by using measured vis-a-vis assumed Hct values. The serial Hct values from 10 patients who were on treatment showed a fluctuation of 15-20% over time. The simulated data showed linear influence of Hct values on kinetic parameters. The tumor grading was altered on altering the Hct values in borderline cases. CONCLUSION: Hct values influence the hemodynamic and kinetic metrics linearly and may affect glioma grading. However, perfusion metrics values might change significantly with large change in Hct values, especially in patients who are on chemotherapy necessitating its use in the DCE model.
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Neoplasias Encefálicas/patología , Medios de Contraste , Glioma/patología , Hematócrito/métodos , Aumento de la Imagen/métodos , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Neoplasias Encefálicas/diagnóstico por imagen , Femenino , Glioma/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION: The resting state functional MRI (rsfMRI) approach is useful to explore the brain's functional organization in health and disease conditions. In this study, using rsfMRI the alteration in brain due to vitamin B12 deficiency and reversibility of these alterations following therapy was studied. METHODS: Thirteen patients with clinical and biochemical evidence of vitamin B12 deficiency were recruited in this study. Fifteen age and sex matched healthy controls were also included. Patients and controls were clinically evaluated using neuropsychological test (NPT). The analysis was carried out using regional homogeneity (ReHo) and low frequency oscillations (LFO) of BOLD signals in resting state. Six patients were also evaluated with rsfMRI and NPT after 6 weeks replacement therapy. RESULTS: ReHo values in patients with vitamin B12 deficiency were significantly lower than controls in the entire cerebrum and the brain networks associated with cognition control, i.e., default mode, cingulo-opercular and fronto-parietal network. There was no significant difference using LFO and it did not show significant correlations with NPT scores. ReHo showed significant correlation with NPT scores. All the 6 patients showed increase in ReHo after replacement therapy. CONCLUSION: We conclude that brain networks associated with cognition control are altered in patients with vitamin B12 deficiency, which partially recover following six weeks of replacement therapy. This is the first study to evaluate the rsfMRI in the light of clinical neuropsychological evaluation in patients. rsfMRI may be used as functional biomarker to assess therapeutic response in vitamin B12 deficiency patients.
Asunto(s)
Encéfalo/fisiopatología , Trastornos del Conocimiento/fisiopatología , Cognición , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Deficiencia de Vitamina B 12/fisiopatología , Adolescente , Adulto , Encéfalo/patología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Red Nerviosa/patología , Red Nerviosa/fisiopatología , Reproducibilidad de los Resultados , Descanso , Sensibilidad y Especificidad , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/diagnóstico , Adulto JovenRESUMEN
We have constructed an Yb-doped fiber laser in all-normal-dispersion configuration which can be independently operated in Q-switched or modelocked configuration with the help of a simple fiber optic ring resonator (FORR). In the presence of FORR, the laser operates in Q-switched mode producing stable pulses in the range of 1 µs-200 ns with repetition rate in the range of 45 kHz-82 kHz. On the other hand, the laser can be easily switched to mode-locked operation by disjoining the FORR loop producing train of ultrashort pulses of â¼5 ps duration (compressible to â¼150 fs) at â¼38 MHz repetition rate. The transmission characteristics of FORR in combination with the nonlinear polarization rotation for passive Q-switching operation is numerically investigated and experimentally verified. The laser can serve as a versatile seed source for power amplifier which can be easily configured for application in the fields that require different pulsed fiber lasers.