Prediction of response to radiotherapy in locally advanced carcinoma cervix using multiparametric MRI: A prospective, single-center, longitudinal study.

PURPOSE: To evaluate the possible role of a multiparametric magnetic resonance imaging (MRI) and semiquantitative fusion map for the prediction of response to radiotherapy in carcinoma cervix. METHODS: This was a prospective, single-center, longitudinal observational study performed on patients with locally advanced carcinoma cervix. Relative blood flow (rBF), relative blood volume (rBV), and apparent diffusion coefficient (ADC) values were obtained before and after the onset of radiotherapy. rBV, rBF, and ADC values were used to generate a semiquantitative pharmacokinetic model map to identify any hypoxic component of the tumor. The subjects were retrospectively classified as responders and nonresponders based on response to treatment. Prospective prediction of response status was done using pretreatment multiparametric MRI parameters (rBF, rBV, and ADC) and semiquantitative parametric map. RESULTS: In 32 patients (29 with parametrial involvement and 15 with lymphadenopathy), pretreatment ADC of the primary tumor was the most accurate measure for predicting response to treatment as well as for treatment-induced fractional volume reduction. Although rBV and rBF were insignificant metrics in isolation for predicting response status, a combination with ADC in the form of parametric map had a sensitivity of 86.4% and 77.2%, specificity of 70% and 70%, positive predictive value of 86.4% and 85%, and negative predictive value 70% and 59% respectively by two independent observers. CONCLUSION: ADC is the most accurate measure for predicting the response to treatment. A manual parametric map generated by an off-line fusion of the above map with those generated by pharmacokinetic modeling of perfusion-weighted MRI may be a useful tool for the prediction of response to radiotherapy.

A prospective randomized comparison of simultaneous integrated boost with sequential boost intensity-modulated radiotherapy in locally advanced head and neck cancer.

Purpose: A comparison of simultaneous integrated boost (SIB) with sequential boost (SEQ) using intensity-modulated radiotherapy along with concurrent cisplatin in locally advanced head and neck cancer (HNC) was made with regard to their survival outcomes and toxicity profile. Materials and Methods: A total of 34 patients were enrolled between October 2016 and March 2019. They were randomized into two arms, SIB and SEQB. All patients were treated with 6 MV photon beam on Linear Accelerator with weekly concurrent cisplatin at 35 mg/m2. Overall survival (OS) and disease-free survival (DFS) were the primary end points and acute and late toxicities were the secondary end points. Results: The median follow-up period was 40.6 and 37.3 months for SIB and SEQB, respectively. At the end of 5 years, the median OS was 40.6 and 37.3 months (P = 0.947) and the median DFS was 35.1 and 37.3 months in the SIB and SEQB arms, respectively (P = 0.991). Complete response at 3 months was 64.7% and 76.5% and partial response was 23.5% and 17.6%, whereas progressive disease was 11.8% and 5.9% in SIB and SEQB arms, respectively. Acute dermatitis, mucositis, dysphagia, and salivary gland toxicities were higher in the SIB arm compared to the SEQB arm. Conclusion: SIB and SEQ arms were comparable in terms of OS and DFS. However, the acute toxicities were higher in the SIB arm, although the difference was not significant, compared to the SEQB arm.

Facet Tropism/Inclination and Its Association with Intervertebral Disc Herniation in the Lumbar Spine - A Radiological Evaluation / Tropismo/inclinação facetária e sua associação com hérnia de disco intervertebral na região lombar da coluna - Uma avaliação radiológica

Abstract Objective To assess the role of facet tropism (FT) in intervertebral disc prolapse. Methods A total 98 patients with lower back pain were included in the study. Magnetic resonance imaging scans were performed and analyzed. The angles of the right and left facets were measured on the axial section. Patients without disc prolapse at the L3-L4, L4-L5 and L5-S1 levels act as controls for those with disc prolapse at the same levels. A statistical analysis was also performed. Results The incidence of FT at the L3-L4 level was of 85.2% in patients with disc herniation (n= 27), and of 56.3% in the control group, which was statistically significant (p= 0.008). Similarly, at the L4-L5 level, incidence of FT among cases and controls was of 71.4% (n= 35) and 52.4% respectively (p= 0.066). At the L5-S1 the incidence was of 66% and 51% among cases and controls respectively (p= 0.13). Conclusion We found a positive association between FT and disc herniation at the L3-L4 level, but no association at the L4-L5 and L5-S1 levels.

Resumo Objetivo Avaliar o papel do tropismo facetário (TF) no prolapso discal intervertebral. Métodos Um total de 98 pacientes com dor lombar foram incluídos no estudo. Exames de ressonância magnética foram realizados e analisados, e os ângulos das facetas direita e esquerda foram medidos na seção axial. Os pacientes sem prolapso discal nos níveis L3-L4, L4-L5 e L5-S1 atuam como controles para aqueles com prolapso nos mesmos níveis. Fez-se também uma análise estatística. Resultados A incidência de TF no nível L3-L4 foi de 85,2% em pacientes com hérnia discal (n= 27), e de 56,3% no grupo controle, o que foi estatisticamente significativo (p= 0,008). Da mesma forma, a incidência de TF no nível L4-L5 entre casos e controles foi de 71,4% (n= 35) e 52,4%, respectivamente (p= 0,066). No nível L5-S1, a incidência foi de 66% e 51% nos caso e nos controles, respectivamente (p= 0,13). Conclusão Encontramos associação positiva entre TF e hérnia de disco no nível L3-L4, mas nenhuma associação nos níveis L4-L5 e L5-S1.

Performance of NI-RADS on CECT Alone to Predict Recurrent Head and Neck Squamous Cell Carcinoma after Chemoradiotherapy: Added Value of RECIST 1.1.

Background The Head and Neck Imaging Reporting and Data System (NI-RADS) is a standardized reporting format for the categorization of the degree of suspicion for recurrent head and neck malignancies on positron emission tomography/computed tomography. Purpose The purpose of our study was to analyze the efficacy of the NI-RADS rating scale and criteria for contrast-enhanced computed tomography (CECT) alone in predicting the local and regional recurrence of malignancies after chemoradiotherapy. Material and Methods CECT of the patients with head and neck cancers receiving radiotherapy and concurrent chemotherapy as a primary treatment was obtained 3 months after the completion of radiotherapy and NI-RADS scoring was done using components of Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria. Their management was guided according to the recommendations based on their NI-RADS score. Results Thirty patients with squamous cell carcinoma of the neck were included in this study. The positive or negative status of the recurrent disease was based on biopsy results or follow-up protocol as recommended in NI-RADS rating scale. Fifteen patients had path proven recurrence at the primary tumor site. For primary tumor site, disease persistence rates of 4% for NI-RADS 1, 24% for NI-RADS 2, and 80% for NI-RADS 3 scores were seen. Five patients had recurrent lymph nodal disease. For lymph nodal assessment, NI-RADS categories 1, 2, and 3 revealed nodal disease recurrence rates of 5.3, 25, and 66.7%, respectively. Conclusion CECT alone may be used to assign the NI-RADS rating scale using RECIST 1.1 criteria to predict the presence or absence of recurrent tumor in patients with neck malignancies.

CT-Based Definition and Structured Reporting of Abdominal Lymph Node Stations.

Background Meticulous evaluation of abdominal lymph nodes on computed tomography (CT) is a fundamental task in radiological practice especially in oncological reporting. Although various reporting systems exist to define abdominal nodal stations for malignancies of individual abdominal organs, a complete and uniform framework for radiological reporting of abdominal lymph nodes does not exist in the literature. Purpose The goal of this review was to provide a step-wise reporting template and precise definitions of the radiological anatomy of abdominal lymph nodes and to generate a CT-based illustration of the lymph node stations of the abdomen. Conclusion This CT-based illustration and reporting template will help the radiologists to aptly describe the extent of the lymph nodal diseases and will help in comparison with posttherapy scans.

Treatment of a genetic brain disease by CNS-wide microglia replacement.

Hematopoietic cell transplantation after myeloablative conditioning has been used to treat various genetic metabolic syndromes but is largely ineffective in diseases affecting the brain presumably due to poor and variable myeloid cell incorporation into the central nervous system. Here, we developed and characterized a near-complete and homogeneous replacement of microglia with bone marrow cells in mice without the need for genetic manipulation of donor or host. The high chimerism resulted from a competitive advantage of scarce donor cells during microglia repopulation rather than enhanced recruitment from the periphery. Hematopoietic stem cells, but not immediate myeloid or monocyte progenitor cells, contained full microglia replacement potency equivalent to whole bone marrow. To explore its therapeutic potential, we applied microglia replacement to a mouse model for Prosaposin deficiency, which is characterized by a progressive neurodegeneration phenotype. We found a reduction of cerebellar neurodegeneration and gliosis in treated brains, improvement of motor and balance impairment, and life span extension even with treatment started in young adulthood. This proof-of-concept study suggests that efficient microglia replacement may have therapeutic efficacy for a variety of neurological diseases.

Comparison of the effects of calcium channel blockers plus iron chelation therapy versus chelation therapy only on iron overload in children and young adults with transfusion-dependent thalassemia: A randomized double-blind placebo-controlled trial.

BACKGROUND: Myocardial iron deposition is a significant cause of morbidity and mortality in patients with transfusion-dependent thalassemia (TDT). Amlodipine, L-type calcium channel blocker with regular chelation therapy may reduce myocardial iron overload. Lack of randomized trials prompted this study to assess the effect of calcium channel blocker (amlodipine) in combination with iron chelation therapy on iron overload in patients with TDT. METHODS: Sixty-four eligible patients were randomized to receive either amlodipine and chelation (group A) or chelation alone (group B) in double-blind placebo-controlled trial. Myocardial iron concentration (MIC) using T2* magnetic resonance imaging (MRI), liver iron concentration (LIC), left ventricular ejection fraction (LVEF), and serum ferritin were measured at baseline and 12 months. RESULTS: In the amlodipine group, mean cardiac T2* value significantly increased from 18.11 ± 8.47 to 22.15 ± 7.61 (p = .002) at 12 months, whereas in control group, there was a nonsignificant increase (p = .62) in cardiac T2* value from 19.50 ± 8.84 to 20.03 ± 9.07. There was a significant decrease in MRI-derived MIC in the amlodipine group compared to control group (1.93 ± 1.61 to 1.29 ± 0.90, p = .01). Changes in the LVEF (p = .45), MRI-derived LIC (p = .09), and serum ferritin (p = .81) were not significant between the two groups. CONCLUSION: Amlodipine is safe and when combined with chelation therapy appears to be more effective in reducing cardiac iron overload than chelation only in children and young adults with TDT.

Bone Mineral Metabolism During Chemotherapy in Childhood Acute Lymphoblastic Leukemia.

OBJECTIVE: The aim of this study was to evaluate levels of vitamin D, bone mineral density (BMD), and radiograph features at diagnosis and after 6 months of chemotherapy in patients with acute lymphoblastic leukemia (ALL). Vitamin D levels were also correlated with BMD and radiograph features. MATERIALS AND METHODS: 25-Hydroxy vitamin D [25(OH)D] levels, BMD, and radiograph features were assessed in 50 newly diagnosed patients of ALL in the age group of 2 to 14 years. A total of 30 age-matched and sex-matched children were recruited as controls. Vitamin D deficiency was defined as 25(OH)D <10 ng/mL, Vitamin D insufficiency as 10 to 29 ng/mL, and Vitamin D sufficiency as ≥30 ng/mL. Enzyme immunoassay (EIA) was used for the quantitative measurement of 25(OH)D levels in plasma and a LUNAR DPX NT bone densitometer was used for the assessment of BMD. RESULTS: The mean age of the patients was 6.3 years, with a male:female ratio of 1.38:1. The mean 25(OH)D levels were 31.90±16.90 ng/mL in patients at diagnosis against 41.63±20.50 ng/mL in controls (P=0.02). Levels were 18.50±11.10 ng/mL postchemotherapy (P=0.00). Female sex was a risk factor for deficient 25(OH)D levels. There was a significant decrease in BMD postchemotherapy in the age groups of 5 to 10 and above 10 years at the femoral neck. Osteopenic changes were observed in more number of patients after 6 months of chemotherapy. There was a significant correlation between vitamin D levels, BMD, and osteopenic changes. CONCLUSIONS: Vitamin D deficiency was common among ALL patients, which worsened after chemotherapy. This had a significant correlation with BMD and osteopenic changes in radiograph.

Utility of Contrast-Enhanced Ultrasound in Differentiation between Benign Mural Lesions and Adenocarcinoma of Gallbladder.

BACKGROUND: Mural lesions of gallbladder on ultrasound (US) are often difficult to characterize as benign or malignant. PURPOSE: The aim of the study was to evaluate the role of contrast-enhanced US (CEUS) in characterization of gallbladder (GB) wall lesions and making distinction between benign wall thickening and GB adenocarcinoma, utilizing both quantitative and qualitative parameters. METHODS: A total of 26 patients with GB wall lesions detected on sonography underwent CEUS. Lesions were evaluated on the basis of morphological imaging features, enhancement pattern, dynamic real-time contrast uptake, and intralesional vascularity. RESULTS: Overall, 19 patients had final diagnosis of GB adenocarcinoma, whereas seven patients had benign etiology. CEUS has enabled the differentiation of nonenhancing tumefactive sludge from enhancing mural lesions, thus improving the accuracy of morphological assessment of lesions. The intactness of outer wall was better assessed on CEUS. The dynamic postcontrast assessment showed that carcinoma showed early washout of contrast compared to benign thickening (P = 0.002). Nonlayered mural enhancement or thick enhancing inner layer with nonenhancing thin outer layer was associated with adenocarcinoma. The classification of intralesional vascularity on CEUS was not helpful in distinguishing benign lesions and adenocarcinoma. CONCLUSION: CEUS can increase the diagnostic confidence in differentiation between benign mural lesions and adenocarcinoma of GB.

Relation Between Cardiac T2* Values and Electrocardiographic Parameters in Children With Transfusion-dependent Thalassemia.

BACKGROUND/OBJECTIVES: Cardiac T2* magnetic resonance imaging (MRI) is the gold standard to determine myocardial iron overload. As availability of Cardiac T2* is not uniform across developing nations, our strategy was to identify a more accessible and cost effective tool to assess myocardial iron accumulation. As children with transfusion-dependent thalassemia also experience various electrocardiographic abnormalities, we performed electrocardiography (ECG) as well as Cardiac T2* MRI on all children registered in our thalassemia unit. MATERIALS AND METHODS: Forty-eight transfusion-dependent thalassemia children with transfusion burden ≥12 times/y (6 to 19 y) in the Thalassemia Unit of the Division of Hematology Oncology, Department of Pediatrics were enrolled. Patients were divided into 3 groups based on severity of T2* value, that is group I (T2*<10), group II (T2* 10 to 20), group III (T2*>20). A T2* value >20 was taken as normal. ECG and serum ferritin was also performed on the day of MRI. RESULTS: Among the various ECG parameters, QRS duration, and QTc interval were significantly increased if cardiac iron overload was high with a P-value of 0.036 and 0.000, respectively. Also, high serum ferritin predicted a decline in T2* value with a P-value of 0.001. QT interval and QTc interval significantly correlated inversely with T2* (P=0.042, r=-0.295 and P=0.002, r=-0.446, respectively) but not QRS duration (P=0.05, r=-0.282). Serum ferritin also was found to have a significant inverse correlation with T2* value (P=0.000, r=-0.497). CONCLUSIONS: Abnormalities on ECG, that is prolongation of QRS duration, QT interval, and QTc interval were significantly associated with cardiac iron overload, that is decrease in the value of Cardiac T2* in our study.

Cardiac T2* magnetic resonance analysis of membranous interventricular septum in assessment of cardiac iron overload in pediatric thalassemia patients: A pilot study.

BACKGROUND: Cardiac iron deposition in transfusion-dependent thalassemia patients is patchy in distribution. PURPOSE: The purpose of this study is to assess the correlation between T2* matrices of membranous interventricular septum (MIVS) and T2* values of muscular interventricular septum (IVS) on magnetic resonance imaging (MRI) and to evaluate the relationship of myocardial T2* at these two locations with MRI-estimated liver iron concentrations (LIC) and electrocardiographic (ECG) parameters. MATERIAL AND METHODS: MRI of heart and liver was performed in 16 consecutive pediatric patients of transfusion-dependent thalassemia major to calculate liver iron concentration and T2* time of membranous and muscular IVS. ECG parameters of these patients were charted and correlated with MRI parameters. RESULTS: No significant correlation between T2* values of muscular IVS and MIVS was observed. Mean T2* of MIVS (9.8 ms) was significantly lower than that of muscular IVS (26.9 ms). T2* of MIVS correlated strongly with LIC where as a weak correlation was observed between T2* of IVS and LIC. Significantly higher mean QTc (corrected QT interval) value (439.86 ms) was seen in patients with T2* IVS <20 ms. CONCLUSION: Addition of T2* analysis of MIVS to the existing MRI protocol, consisting of muscular IVS analysis, may offer a more sensitive estimation of cardiac iron overload.

Posterior quadrantic dysplasia with localized hemimegalencephaly in a patient with giant congenital melanocytic nevus: First case report.

Giant congenital melanocytic nevus (GCMN) is associated with neurocutaneous melanocytosis and various other neurological complications. Its association with migrational anomalies of the brain is extremely rare. Herein, we document the first case of GCMN in a one-day-old baby associated with localized hemimegalencephaly (HME) of the brain with extensive malformation of cortical development including polymicrogyria, pachygyria and sublobar dysplasia, limited to an enlarged quadrant of the brain. HME and GCMN are considered embryological anomalies of cell migration and proliferation. We discuss the unusual magnetic resonance imaging findings along with a brief review of the literature. To the best of our knowledge, our case is the first to report the association of GCMN with localized HME.

Performance of quantitative CT parameters in assessment of disease severity in COPD: A prospective study.

BACKGROUND: Both emphysematous destruction of lung parenchyma and airway remodeling is thought to contribute to airflow limitation in cases of chronic obstructive pulmonary disease (COPD). OBJECTIVE: To evaluate the value of quantitative computed tomography (QCT) parameters of emphysema and airway disease with disease severity in patients with COPD. MATERIALS AND METHODS: We prospectively studied 50 patients with COPD, which included nonsmokers and patients with different degrees of cumulative smoking exposure. Three QCT parameters namely LAA% (low attenuation area percentage), WA% (Wall area percentage), and pi10 were calculated as per the standard technique. Forced expiratory volume in 1 s (FEV1), BODE score, and MMRC dyspnea scale were used as measures of disease severity. RESULTS: FEV1 was inversely and significantly associated with all three QCT parameters. Receiver operated characteristic curves in prediction of GOLD class 3 COPD yielded cut-off values of 12.2, 61.45, and 3.5 for LAA%, WA%, and pi10, respectively, with high sensitivities and specificities. In multiple linear regression model, however, only LAA% proved to be significantly associated with FEV1, BODE, and dyspnea. CONCLUSION: QCT indices of both emphysema and airway disease influence FEV1, dyspnea, and BODE score in patients with COPD. Emphysema, however, appears to be more closely related to disease severity.

A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs.

Polycomb group proteins regulate self-renewal and differentiation in many stem cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they sequentially deposit H3K27me3 and H2AK119ub histone marks and establish repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of accessory subunits. How these non-canonical complexes recognize and regulate their gene targets remains poorly understood. Here, we show that the BCL6 co-repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to the erosion of Polycomb domains at key developmental loci and the initiation of differentiation along endoderm and mesoderm lineages. The C terminus of BCOR regulates the assembly and targeting of the PRC1.1 complex, while the N terminus contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding of Polycomb targeting and repression in ESCs and could apply broadly across developmental systems.

Multimodality imaging of vaginal rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a malignant mesenchymal tumor arising from the embryonal muscle cells (rhabdomyoblasts), and is the most common soft tissue sarcoma in children and young adults accounting for 4-6% of all malignancies in this age group. Though rare overall, embryonal rhabdomyosarcoma is the most common malignancy arising in the pediatric female genitourinary tract with sarcoma botryoides being the most common variant of the tumor. In young and adolescent individuals, the cervix and uterus are affected; whereas in infants, vaginal lesions are more common. Imaging plays a crucial role not only in the initial diagnosis but also in long-term follow-up of genital RMS. We describe a rare case of embryonal rhabdomyosarcoma of the vagina occurring in a 23-year-old female who presented with abnormal vaginal bleeding ever since she was a child.

Magnetic resonance neurographic confirmation of extensive Plexiform neurofibroma in neurofibromatosis-1 presenting as ambiguous genitalia.

Genitourinary involvement of neurofibromatosis is uncommon and genital neurofibromatosis is even rarer. Involvement of clitoris by neurofibroma can lead to clitoromegaly masquerading as a male penis. We report such a case of ambiguous genitalia in a 7-year-old female child presenting with clitoromegaly since birth, in which magnetic resonance imaging (MRI) revealed the presence of extensive neurofibromatosis in the clitoris and lumbosacral regions. We emphasize the central role of MRI in evaluation of hormonal and non-hormonal causes of ambiguous genitalia. We further discuss the merits of including MR neurography in the imaging protocol for comprehensive delineation of neurofibromatosis.

Magnetic resonance spectroscopy - Revisiting the biochemical and molecular milieu of brain tumors.

BACKGROUND: Magnetic resonance spectroscopy (MRS) is an established tool for in-vivo evaluation of the biochemical basis of human diseases. On one hand, such lucid depiction of 'live biochemistry' helps one to decipher the true nature of the pathology while on the other hand one can track the response to therapy at sub-cellular level. Brain tumors have been an area of continuous interrogation and instigation for mankind. Evaluation of these lesions by MRS plays a crucial role in the two aspects of disease management described above. SCOPE OF REVIEW: Presented is an overview of the window provided by MRS into the biochemical aspects of brain tumors. We systematically visit each metabolite deciphered by MRS and discuss the role of deconvoluting the biochemical aspects of pathologies (here in context of brain tumors) in the disease management cycle. We further try to unify a radiologist's perspective of disease with that of a biochemist to prove the point that preclinical work is the mother of the treatment we provide at bedside as clinicians. Furthermore, an integrated approach by various scientific experts help resolve a query encountered in everyday practice. MAJOR CONCLUSIONS: MR spectroscopy is an integral tool for evaluation and systematic follow-up of brain tumors. A deeper understanding of this technology by a biochemist would help in a swift and more logical development of the technique while a close collaboration with radiologist would enable definitive application of the same. GENERAL SIGNIFICANCE: The review aims at inciting closer ties between the two specialists enabling a deeper understanding of this valuable technology.

Mandibular arteriovenous malformation: A rare life-threatening condition depicted on multidetector CT angiography.

Arteriovenous malformation (AVM) of the mandible is a rare and potentially life-threatening condition which can lead to massive hemorrhage. The following is a description where a large mandibular AVM presented with torrential bleeding following tooth extraction for caries. An orthopantomogram (OPG) was performed which was suggestive of aneurysmal bone cyst or ameloblastoma. A computed tomography (CT) angiography revealed a large mandibular AVM with submandibular extension. It is important for both clinicians and radiologist to be aware of this type of lesion that can have life-threatening complications. It is important to define the anatomical location and the feeder vessels of the entity in detail preoperatively. This communication highlights the common differential and use of multidetector CT (MDCT) angiography along with other imaging modalities to prevent a fatal hemorrhage and arrive at a correct diagnosis.