Evaluation of VMAT Planning Strategies for Prostate Patients with Bilateral Hip Prosthesis.

Purpose: In this study, we investigate linac volumetric-modulated arc therapy (VMAT) planning strategies for bilateral hip prostheses prostate patients with respect to plan quality and deliverability, while limiting entrance dose to the prostheses. Methods: Three VMAT plans were retrospectively created for 20 patients: (1) partial arcs (PA), (2) 2 full arcs optimized with 500 cGy max prostheses dose (MD), and (3) 2 full arcs optimized with max dose-volume histogram (DVH) constraint of 500 cGy to 10% prostheses volume (MDVH). PA techniques contained 6 PA with beam angles that avoid entering each prosthesis. For each patient, other than prostheses constraints, the same Pinnacle VMAT optimization objectives were used. Plans were normalized with PTV D95% = 79.2 Gy prescription dose. Organ-at-risk DVH metrics, monitor units (MUs), conformality, gradient, and homogeneity indices were evaluated for each plan. Mean entrance prosthesis dose was determined in Pinnacle by converting each arc into static beams and utilizing only control points traversing each prosthesis. Plan deliverability was evaluated with SunNuclear ArcCheck measurements (gamma criteria 3%/2 mm) on an Elekta machine. Results: MD and MDVH had similar dosimetric quality, both improved DVH metrics for rectum and bladder compared to PA. Plan complexities among all plans were similar (average MUs: 441-518). Conformality, homogeneity, and gradient indices were significantly improved in MD and MDVH versus PA (P < .001). Gamma pass rates for MD (99.0 ± 1.2%) and MDVH (99.2 ± 0.99%) were comparable. A significant difference over PA was observed (96.8 ± 1.6%, P < .001). Field-by-field analysis demonstrated 12/20 PA plans resulted in fields with pass rates <95% versus 1/20 plans for MD and none for MDVH. Cumulative mean entrance doses to each prosthesis were 62.9 ± 17.7 cGy for MD plans and 83.4 ± 27.5 cGy for MDVH plans. Conclusion: MD and MDVH plans had improved dosimetric quality and deliverability over PA plans with minimal entrance doses (∼1% of prescription) to each prosthesis and are an improved alternative for bilateral prostheses prostate patients.

Investigating the dosimetric effects of grid size on dose calculation accuracy using volumetric modulated arc therapy in spine stereotactic radiosurgery.

PURPOSE: Sharp dose gradients between the target and the spinal cord are critical to achieve dose constraints in spine stereotactic radiosurgery (SRS), however the accuracy of the doses to the spinal cord at these high dose gradients is sensitive to the how the dose is sampled across the structure using a discretized isotropic calculation grid. In this study, the effect of the grid size (GS) on the dosimetric accuracy of volumetric modulated arc therapy (VMAT) spine SRS plans was investigated. METHODS: The Eclipse v11.0 Anisotropic Analytical Algorithm (AAA) algorithm was used for dose calculation. Plan qualities of fifty treatment plans were evaluated with a GS of 2.5 (AAA's default value), 1.5 and 1mm. All plans were prescribed to the 90% isodose line in 1 fraction. Parameters used for plan comparison included the distance-to-fall-off (DTF) between the 90% and 50% isodose levels in the axial plane, planning tumor volume (PTV) coverage to 99%, 95%, 5% and 0.03cc, dose to 10% (Cord_D10%) and 0.03cc (Cord_D0.03cc) of the spinal cord sub volume. The dosimetric accuracy was evaluated based on film dosimetry percent gamma pass rate, line profile through the cord. Calculation times between different grid sizes as well as DVH algorithm differences between two treatment planning systems (Eclipse vs Velocity) were compared. Paired t-test was used to investigate the statistical significance. RESULTS: The DTF decreased for all plans with 1mm compared to 1.5mm and 2.5mm GS (2.52±0.54mm, 2.83±0.58mm, 3.30±0.64, p<0.001). Relative to the 1mm GS, Cord_D0.03cc and Cord_D10% increased by 6.24% and 7.81% with the 1.5mm GS, and 9.80% and 13% with the 2.5mm GS. Film analysis demonstrated higher gamma pass rates for 1.5mm GS compared to 1 and 2.5mm GS (95.9%±5.4%, 94.3%±6.0%, 93.6%±5.4%, p<0.001), however 1mm GS showed better agreement in the high dose gradient near the cord. Calculation times for 1mm GS plans increased for 1.5 and 2.5mm GS (61% and 84%, p<0.001). The average difference between the two treatment planning systems was approximately 0-1.2%. A maximum difference of 5.9% occurred for Cord_D0.03cc for the 1mm GS. CONCLUSION: Plans calculated with a 1mm grid size resulted in the most accurate representation of the dose delivered to the cord, however resulted in less uniform dose distributions in the high dose region of the PTV. The use of a 1.5mm grid size may balance accurate cord dose and PTV coverage, while also being more practical with respect to computation time.

[Significance of Th17/Treg imbalance in children with primary immune thrombocytopenia].

OBJECTIVE: To investigate the significance of Th17/Treg imbalance in the development and treatment of primary immune thrombocytopenia (ITP) in children. METHODS: Thirty-two children diagnosed with ITP between May and August, 2015 and 22 healthy children were enrolled. Flow cytometry was used to determine the Th17/Treg ratio in peripheral blood of healthy children and children with ITP before and after treatment with immunoglobulin. RESULTS: Compared with the patients with ITP before treatment, the healthy children and the patients treated with immunoglobulin had a significantly lower percentage of Th17 cells in CD4+ T cells, a significantly lower Th17/Treg ratio, and a significantly higher percentage of Treg cells in CD4+ T cells in peripheral blood (P<0.05). In the 32 ITP children treated with immunoglobulin, 20 had complete response, 4 had response, and 8 had no response. The patients with complete response had a significantly lower percentage of Th17 cells in CD4+ T cells and a significantly lower Th17/Treg ratio in peripheral blood than the patients without response (P<0.05). CONCLUSIONS: The Th17/Treg imbalance can be found in children with ITP. Immunoglobulin can improve the cellular immune function by regulation of the Th17/Treg ratio. The Th17/Treg ratio may serve as an indicator for assessing the therapeutic effects of ITP.

Assessing global and regional iron content in deep gray matter as a function of age using susceptibility mapping.

PURPOSE: To investigate the correlation of non-heme iron content in deep gray matter nuclei as a function of age using quantitative susceptibility mapping (QSM) from both whole-structural and regional perspectives. MATERIALS AND METHODS: We studied a group of 174 normal subjects ranging from 20 to 69 years old and measured the magnetic susceptibility of seven subcortical gray matter nuclei. SWI (susceptibility-weighted imaging) phase images were used to generate the susceptibility maps, which were acquired on a 1.5T scanner. The 3D whole-structural measurements were used to determine age-related thresholds, which were applied to calculate the local iron deposition (RII: portion of the structure that contains iron concentration larger than the structure threshold). Age-susceptibility correlation was reported for each measured structure for both the whole-region and two-region (low iron and high iron content regions) analysis. RESULTS: For the local high iron content region, a strong age-susceptibility correlation was found in the caudate nucleus (CN,R = 0.9), putamen (PUT,R = 0.9), red nucleus (RN,R = 0.8), globus pallidus (GP,R = 0.7), substantia nigra (SN,R = 0.5), and pulvinar thalamus (PT,R = 0.5); for the global iron content, a strong age-susceptibility correlation was found in CN(R = 0.6), PUT(R = 0.7), and RN(R = 0.6). Overall, for each structure analyzed in this study, regional analysis showed higher correlation coefficient and higher slope comparing to the whole-region analysis. Further, we found the quantitative conversion factor between magnetic susceptibility and iron concentration to be 1.03 ± 0.03 ppb per µg iron/g wet tissue. CONCLUSION: We conclude that the age-susceptibility correlation can serve as a quantitative magnetic susceptibility baseline as a function of age for monitoring abnormal global and regional iron deposition. A regional analysis has shown a tighter age related behavior, providing a reliable and sensitive reference for what can be considered normal iron content for studies of neurodegenerative diseases. J. Magn. Reson. Imaging 2016;44:59-71.

Iron Accumulation Is Not Homogenous among Patients with Parkinson's Disease.

Background. Iron is considered to lead to neurodegeneration and has been hypothesized as a possible cause of Parkinson's disease (PD). Susceptibility-weighted imaging (SWI) is a powerful tool to measure phase related iron content of brain. Methods. Twelve de novo patients with PD were recruited from the Movement Disorders Clinic, Department of Neurology, Loma Linda University. Twelve age- and sex-matched non-PD subjects were recruited from neurology clinic as controls. Using SWI, the phase related iron content was estimated from different brain regions of interest (ROIs). Results. There was a trend between increasing age and iron accumulation in the globus pallidus and putamen in all subjects. Iron accumulation was not significant in different ROIs in PD patients compared to controls after adjustment for age. Our data revealed heterogeneity of phase values in different brain ROIs among all subjects with an exaggerated trend at SN in PD patients. Conclusions. Our data suggest a nonhomogeneous pattern of iron accumulation in different brain regions among PD patients. Further studies are needed to explore whether this may correlate to the progression of PD. To our knowledge, this is the first study demonstrating the heterogeneity of iron accumulation in the brain, among patients with PD.

Quantifying brain iron deposition in patients with Parkinson's disease using quantitative susceptibility mapping, R2 and R2.

PURPOSE: To evaluate the sensitivity and specificity of quantitative magnetic resonance (MR) iron mapping including R2, R2* and magnetic susceptibility to differentiate patients with Parkinson's disease (PD) from healthy controls. MATERIALS AND METHODS: Thirty (30) healthy controls (HC) (64±7years old) and 20 patients with idiopathic PD (66±8years old) were studied using a 3T MR imaging scanner. R2 maps were generated from GRASE sequence while R2*, and quantitative susceptibility mapping (QSM) were obtained from a conventional multi-echo gradient-echo sequence. R2, R2* and relative susceptibility (Δχ) values of structures in the basal ganglia were measured for each patient and control. An analysis of sensitivity and specificity and unpaired t-test was applied to the two groups. RESULTS: A significant difference (p<0.05) was found for R2 and ∆χ values in the substantia nigra as a whole and in the pars compacta for PD patients. The R2* values were different significantly (p<0.05) only on the substantia nigra pars compacta. QSM presented the highest sensitivity and specificity to differentiate the two populations. CONCLUSION: The QSM map was the most sensitive quantitative technique for detecting a significant increase of iron for PD. The highest significant difference between controls and patients was found in the substantia nigra pars compacta using QSM.

[Clinical features of childhood hemophagocytic syndrome and its association with human parvovirus B19 infection].

OBJECTIVE: To investigate the association of childhood hemophagocytic syndrome (HPS) with human parvovirus B19 (HPVB19) infection, and to analyze the clinical features of this disease. METHODS: ELISA and quantitative real-time PCR were used to detect HPVB19-IgM, HPVB19-IgG and HPVB19-DNA in 65 children with HPS (HPS group) and 65 healthy children (control group). The HPS group was divided into HPVB19-infected (n=14) and non-infected (n=51) groups according to the detection results of HPVB19-DNA. The clinical data of two groups were compared. RESULTS: The positive rate of HPVB19-IgM in the HPS group (26%, 17/65) was significantly higher than that in the control group (9%, 6/65) (P=0.011), and there was no significant difference in the positive rate of HPVB19-IgG between the HPS (38%, 25/65) and control groups (29%, 19/65) (P=0.266). The infection rate of HPVB19 in the HPS group (22%, 14/65) was significantly higher than that in the control group (3%, 2/65) (P=0.001). Compared with the non-infected group, the HPVB19-infected group had significantly lower platelet count and hemoglobin level on admission, significantly more severe liver function damage, a significantly earlier onset time, and a significantly longer course of disease (P<0.05). CONCLUSIONS: The pathogenesis of HPS may be associated with HPVBl9 infection. HPVBl9-infected children with HPS have more acute onset, more severe clinical manifestations, and a longer disease duration.

Patterns of chronic venous insufficiency in the dural sinuses and extracranial draining veins and their relationship with white matter hyperintensities for patients with Parkinson's disease.

BACKGROUND: Idiopathic Parkinson's disease (IPD) remains one of those neurodegenerative diseases for which the cause remains unknown. Many clinically diagnosed cases of IPD are associated with cerebrovascular disease and white matter hyperintensities (WMHs). The purpose of this study was to investigate the presence of transverse sinus and extracranial venous abnormalities in IPD patients and their relationship with brain WMHs. METHODS: Twenty-three IPD patients and 23 age-matched normal controls were recruited in this study. They had conventional neurologic magnetic resonance structural and angiographic scans and, for blood flow, quantification of the extracranial vessels. Venous structures were evaluated with two-dimensional time of flight; flow was evaluated with two-dimensional phase contrast; and WMH volume was quantified with T2-weighted fluid-attenuated inversion recovery. The IPD and normal subjects were classified by both the magnetic resonance time-of-flight and phase contrast images into four categories: (1) complete or local missing transverse sinus and internal jugular veins on the time-of-flight images; (2) low flow in the transverse sinus and stenotic internal jugular veins; (3) reduced flow in the internal jugular veins; and (4) normal flow and no stenosis. RESULTS: Broken into the four categories with categories 1 to 3 combined, a significant difference in the distribution of the IPD patients and normal controls (χ(2) = 7.7; P < .01) was observed. Venous abnormalities (categories 1, 2, and 3) were seen in 57% of IPD subjects and in only 30% of controls. In IPD subjects, category type correlated with both flow abnormalities and WMHs. CONCLUSIONS: From this preliminary study, we conclude that a major fraction of IPD patients appear to have abnormal venous anatomy and flow on the left side of the brain and neck and that the flow abnormalities appear to correlate with WMH volume. Studies with a larger sample size are still needed to confirm these findings.

Evaluation of the deformation and corresponding dosimetric implications in prostate cancer treatment.

The cone-beam computed tomography (CBCT) imaging modality is an integral component of image-guided adaptive radiation therapy (IGART), which uses patient-specific dynamic/temporal information for potential treatment plan modification. In this study, an offline process for the integral component IGART framework has been implemented that consists of deformable image registration (DIR) and its validation, dose reconstruction, dose accumulation and dose verification. This study compares the differences between planned and estimated delivered doses under an IGART framework of five patients undergoing prostate cancer radiation therapy. The dose calculation accuracy on CBCT was verified by measurements made in a Rando pelvic phantom. The accuracy of DIR on patient image sets was evaluated in three ways: landmark matching with fiducial markers, visual image evaluation and unbalanced energy (UE); UE has been previously demonstrated to be a feasible method for the validation of DIR accuracy at a voxel level. The dose calculated on each CBCT image set was reconstructed and accumulated over all fractions to reflect the 'actual dose' delivered to the patient. The deformably accumulated (delivered) plans were then compared to the original (static) plans to evaluate tumor and normal tissue dose discrepancies. The results support the utility of adaptive planning, which can be used to fully elucidate the dosimetric impact based on the simulated delivered dose to achieve the desired tumor control and normal tissue sparing, which may be of particular importance in the context of hypofractionated radiotherapy regimens.

Diagnostic value of diffusion-weighted magnetic resonance imaging compared with fluorodeoxyglucose positron emission tomography/computed tomography for pancreatic malignancy: a meta-analysis using a hierarchical regression model.

BACKGROUND AND AIM: To obtain diagnostic performance of diffusion-weighted magnetic resonance imaging (DWI) and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the detection of pancreatic malignancy. METHODS: We performed a meta-analysis of all available studies of the diagnostic performance of DWI and PET/CT for pancreatic malignancy. MEDLINE, EMBASE, Cochrane library and some other databases were searched for initial studies. We determined sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves (SROC) using hierarchical regression models. RESULTS: Across 16 studies with 804 patients, PET/CT sensitivity was 0.87 (95% confidence interval [CI], 0.82, 0.81) and specificity was 0.83 (95% CI, 0.71, 0.91). Overall, LR+ was 5.84 (95% CI, 4.59, 7.42) and LR- was 0.24 (95% CI, 0.17, 0.33). DWI sensitivity was 0.85 (95% CI, 0.74, 0.92) and specificity was 0.91 (95% CI, 0.71, 0.98). LR+ was 9.53 (95% CI, 2.41, 37.65) and LR- was 0.17 (95% CI, 0.09, 0.32). In subgroup analysis, the sensitivity of enhanced versus unenhanced PET/CT in the detection of pancreatic cancer was 0.91 (95% CI, 0.86, 0.96) versus 0.84 (95% CI, 0.78, 0.90) (P > 0.05), the specificity 0.88 (95% CI, 0.73, 1.00) versus 0.81 (95% CI, 0.69, 0.94) (P > 0.05). CONCLUSION: Positron emission tomography/computed tomography (PET/CT) was highly sensitive and DWI was a highly specific modality in diagnosing patients with pancreatic malignancy. PET/CT and DWI could play different roles in diagnosing pancreatic carcinoma. Enhanced PET/CT seems to be superior to unenhanced PET/CT. Further larger prospective studies are needed to establish its value for diagnosis in pancreatic cancer.

Value of magnetic resonance imaging for nodal staging in patients with head and neck squamous cell carcinoma: a meta-analysis.

OBJECTIVES: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting lymph node metastases in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: MEDLINE, EMBASE, the CBM disc databases, and other databases were searched for relevant original articles published between January 1990 and January 2011. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver-operating characteristic, and to calculate positive and negative likelihood ratios (LR+ and LR-). We also compared the performance of MRI with other diagnostic methods (positron emission tomography, computed tomography, and ultrasound) by analyzing studies that had also used these diagnostic methods on the same patients. RESULTS: Across 16 studies, there was no evidence of publication bias (P = .15). Sensitivity and specificity of MRI for cervical lymph node status in patients with HNSCC across all studies were 76% (95% CI: 70%-82%) and 86% (95% CI: 73%-93%), respectively. Overall, Positive likelihood ratios was 5.47 (95% CI: 2.69-11.11) and positive negative likelihood ratios was 0.28 (95% CI: 0.21-0.36), respectively. The comparison of MRI performance with that of other diagnostic tools (positron emission tomography, computed tomography, and ultrasound) suggested no major differences against any of these methods. The Subgroup by using diffusion-weighted imaging had higher pooled sensitivity (0.86, 95% CI 0.78-0.92) than the subgroup without diffusion-weighted imaging. CONCLUSION: MRI has good diagnostic performance in the overall pretreatment evaluation of node staging with HNSCC. A limited number of small studies suggest DWI is superior to conventional imaging for nodal staging of HNSCC.

Correlation of putative iron content as represented by changes in R2* and phase with age in deep gray matter of healthy adults.

PURPOSE: To establish a correlation between putative iron content using susceptibility weighted imaging (SWI) phase and T2* weighted magnitude values in the basal ganglia and the thalamus as a function of age in healthy human brains. MATERIALS AND METHODS: One hundred healthy adults (range, 20-69 years; mean, 43 years) were evaluated for this study using a gradient echo sequence. The original magnitude and high pass filtered phase data were analyzed as proxy variables for iron content in the substantia nigra, red nucleus, globus pallidus, putamen, caudate nucleus, thalamus, and pulvinar thalamus. Each structure was broken into two parts, a high iron content region and a low iron content region. RESULTS: Both magnitude and phase data showed an increase in putative iron content with age. However, the high iron content region revealed two new pieces of information: both the average iron content per pixel and the area of high iron increased with age. Furthermore, significant increase in iron uptake as a function of age was found past the age of 40. CONCLUSION: A two region of interest analysis of iron is a much more sensitive means to evaluate iron content change over time. Contrary to the current belief that iron content increases level off with age, the putative iron deposition in the high iron content region is seen to increase with age.