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Introduction: Structural brain alterations in pain-related areas have been demonstrated in patients with non-specific neck pain. While manual therapy combined with therapeutic exercise is an effective management for neck pain, its underlying mechanisms are poorly understood. The primary objective of this trial is to investigate the effects of manual therapy combined with therapeutic exercise on grey matter volume and thickness in patients with chronic non-specific neck pain. The secondary objectives are to assess changes in white matter integrity, neurochemical biomarkers, clinical features of neck pain, cervical range of motion and cervical muscle strength., Methods and Analysis: This study is a single-blinded, randomised controlled trial. Fifty-two participants with chronic non-specific neck pain will be recruited into the study. Participants will be randomly allocated to either an intervention or control group (1:1 ratio). Participants in the intervention group will receive manual therapy combined with therapeutic exercise for 10 weeks (two visits per week). The control group will receive routine physical therapy. Primary outcomes are whole-brain and regional grey matter volume and thickness. Secondary outcomes are white matter integrity (fractional anisotropy and mean diffusivity), neurochemical biomarkers (N-acetylaspartate, creatine, glutamate/glutamine, myoinositol and choline), clinical features (neck pain intensity, duration, neck disability and psychological symptoms), cervical range of motion and cervical muscle strength. All outcome measures will be taken at baseline and postintervention., Ethics and Dissemination: Ethical approval of this study has been granted by Faculty of Associated Medical Science, Chiang Mai University. The results of this trial will be disseminated through a peer-reviewed publication., Trial Registration Number: NCT05568394., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Scan time reduction is necessary for volumetric acquisitions to improve workflow productivity and to reduce motion artifacts during MRI procedures. We explored the possibility that Compressed Sensing-4 (CS-4) can be employed with 3D-turbo-field-echo T1-weighted (3D-TFE-T1W) sequence without compromising subcortical measurements on clinical 1.5 T MRI., Materials and Methods: Thirty-three healthy volunteers (24 females, 9 males) underwent imaging scans on a 1.5 T MRI equipped with a 12-channel head coil. 3D-TFE-T1W for whole-brain coverage was performed with different acceleration factors, including SENSE-2, SENSE-4, CS-4. Freesurfer, FSL's FIRST, and volBrain packages were utilized for subcortical segmentation. All processed data were assessed using the Wilcoxon signed-rank test., Results: The results obtained from SENSE-2 were considered as references. For SENSE-4, the maximum signal-to-noise ratio (SNR) drop was detected in the Accumbens (51.96%). For CS-4, the maximum SNR drop was detected in the Amygdala (10.55%). Since the SNR drop in CS-4 is relatively small, the SNR in all of the subcortical volumes obtained from SENSE-2 and CS-4 are not statistically different (P > 0.05), and their Pearson's correlation coefficients are larger than 0.90. The maximum biases of SENSE-4 and CS-4 were found in the Thalamus with the mean of differences of 1.60 ml and 0.18 ml, respectively., Conclusion: CS-4 provided sufficient quality of 3D-TFE-T1W images for 1.5 T MRI equipped with a 12-channel receiver coil. Subcortical volumes obtained from the CS-4 images are consistent among different post-processing packages., (© 2021. European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

Background: To estimate median liver iron concentration (LIC) calculated from magnetic resonance imaging, excluded vessels of the liver parenchyma region were defined manually. Previous works proposed the automated method for excluding vessels from the liver region. However, only user-defined liver region remained a manual process. Therefore, this work aimed to develop an automated liver region segmentation technique to automate the whole process of median LIC calculation., Methods: 553 MR examinations from 471 thalassemia major patients were used in this study. LIC maps (in mg/g dry weight) were calculated and used as the input of segmentation procedures. Anatomical landmark data were detected and used to restrict ROI. After that, the liver region was segmented using fuzzy c-means clustering and reduced segmentation errors by morphological processes. According to the clinical application, erosion with a suitable size of the structuring element was applied to reduce the segmented liver region to avoid uncertainty around the edge of the liver. The segmentation results were evaluated by comparing with manual segmentation performed by a board-certified radiologist., Results: The proposed method was able to produce a good grade output in approximately 81% of all data. Approximately 11% of all data required an easy modification step. The rest of the output, approximately 8%, was an unsuccessful grade and required manual intervention by a user. For the evaluation matrices, percent dice similarity coefficient (%DSC) was in the range 86-92, percent Jaccard index (%JC) was 78-86, and Hausdorff distance (H) was 14-28 mm, respectively. In this study, percent false positive (%FP) and percent false negative (%FN) were applied to evaluate under- and over-segmentation that other evaluation matrices could not handle. The average of operation times could be reduced from 10 s per case using traditional method, to 1.5 s per case using our proposed method., Conclusion: The experimental results showed that the proposed method provided an effective automated liver segmentation technique, which can be applied clinically for automated median LIC calculation in thalassemia major patients., (© 2021. The Author(s).)

Background: Iron overload cardiomyopathy is the most common cause of death in patients with transfusion-dependent thalassemia., Aim: The aim of this study was to determine the efficacy of carvedilol treatment in patients with transfusion-dependent thalassemia who had left ventricular diastolic dysfunction., Methods: Eighteen patients with transfusion-dependent thalassemia who had left ventricular diastolic dysfunction were enrolled. All patients had normal left ventricular systolic function and were given carvedilol with the target dose of 0.8 mg/kg/day. Ventricular function and the level of cardiac iron were assessed by echocardiography and magnetic resonance imaging at 0, 3, and 6 months., Results: The median age of the patients was 19 years (range 13-25 years). Four patients had severe left ventricular Grade III diastolic dysfunction and fourteen patients had Grade II diastolic dysfunction. The grade of left ventricular diastolic dysfunction was improved at 3 months after the carvedilol treatment. The Doppler parameters, including pulmonary vein atrial reversal velocity, pulmonary vein atrial reversal duration, and the difference of pulmonary vein atrial reversal and the mitral valve atrial contraction wave duration at 3 months after the carvedilol treatment, were significantly lower than these parameters before the treatment., Conclusions: Among patients with transfusion-dependent thalassemia who had left ventricular diastolic dysfunction without systolic dysfunction, treatment with carvedilol for 3 months was associated with improvement in Doppler parameters of left ventricular diastolic function. However, this finding and its clinical significance need to be confirmed in further double-blind controlled studies., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Annals of Pediatric Cardiology.)

Cardiac T2* MRI is used as a gold standard for cardiac iron quantification in patients with transfusion-dependent thalassemia (TDT). We hypothesized that left ventricular (LV) diastolic dysfunction would reflect the severity of iron overload and can serve as an early detection of cardiac iron deposits. A study was conducted on all patients with TDT. Hemoglobin, serum ferritin and non-transferrin bound iron, together with a complete echocardiography and cardiac T2* MRI, were performed on all patients. Seventy-seven patients with TDT were enrolled (median age 14 years). In the patient group with a mean serum ferritin of > 2500 ng/mL during the past 12 months, there were more patients with severe cardiac iron deposits than in the group with a mean serum ferritin of ≤ 2500 ng/mL. Diastolic dysfunction was absent in all patients with a serum ferritin of < 1000 ng/mL. All patients with cardiac T2* ≤ 20 ms had grade III LV diastolic dysfunction. However, twenty-one percent of patients with cardiac T2* > 20 ms had LV diastolic dysfunction. The differences observed in pulmonary vein atrial reversal duration and mitral A-wave (PVAR-MVA) duration ≥ - 1 ms and an E/E' ratio ≥ 11 were proven to be the associated factors with the cardiac T2* ≤ 20 ms. Increased PVAR-MVA duration and increased E/E' ratio reliably reflected a severe iron overload, according to a cardiac T2* in patients with TDT. LV diastolic dysfunction can occur prior to severe cardiac iron deposition. Tissue Doppler echocardiography has the potential for the early detection of cardiac involvement in patients with TDT .

Background: Vitamin D deficiency is common in patients with thalassemia. Vitamin D deficiency could be related to cardiac dysfunction. Increased parathyroid hormone (PTH) is also known to be associated with heart failure., Objectives: To determine the prevalence of Vitamin D deficiency and to explore the impact of Vitamin D deficiency on cardiac iron and function in patients with transfusion-dependent thalassemia., Method: A cross-sectional study in patients with Transfusion-dependent thalassemia was conducted. Patients with liver disease, renal disease, type 1 diabetes, malabsorption, hypercortisolism, malignancy, and contraindication for MRI were excluded. Calcium, phosphate, PTH, vitamin D-25OH were measured. CardiacT2 * and liver iron concentration (LIC) and left ventricular ejection fraction (LVEF) were determined. Results Sixty-one (33M/28F) patients with Transfusion-dependent thalassemia were enrolled. The prevalence of Vitamin D deficiency was 50.8%. Patients with cardiac siderosis had tendency for lower D-25OH than those without siderosis (15.9 (11.7-20.0) vs. 20.2 (15.85-22.3) ng/mL); p = 0.06). Serum calcium, phosphate, PTH, LIC, cardiac T2 * , and LVEF were not different between the groups with or without Vitamin D deficiency. Patients with Vitamin D deficiency had significantly lower hemoglobin levels compared to those without Vitamin D deficiency (7.5 (6.93-8.33) vs. 8.1 (7.30-8.50) g/dL; p = 0.04). The median hemoglobin in the last 12 months was significantly correlated with D-25OH. Cardiac T2 * had significant correlation with PTH., Conclusion: Vitamin D deficiency is prevalent in patients with Transfusion-dependent thalassemia. Vitamin D level is correlated with hemoglobin level. Vitamin D status should be routinely assessed in these patients. Low PTH is correlated with increased cardiac iron. This study did not demonstrate an association between Vitamin D deficiency and cardiac iron or function in patients with Transfusion-dependent thalassemia.

Purpose: To develop an in-house software program that is able to calculate and generate the biological dose distribution and biological dose volume histogram by physical dose conversion using the linear-quadratic-linear (LQL) model., Material and Methods: The Isobio software was developed using MATLAB version 2014b to calculate and generate the biological dose distribution and biological dose volume histograms. The physical dose from each voxel in treatment planning was extracted through Computational Environment for Radiotherapy Research (CERR), and the accuracy was verified by the differentiation between the dose volume histogram from CERR and the treatment planning system. An equivalent dose in 2 Gy fraction (EQD 2 ) was calculated using biological effective dose (BED) based on the LQL model. The software calculation and the manual calculation were compared for EQD 2 verification with pair t -test statistical analysis using IBM SPSS Statistics version 22 (64-bit)., Results: Two and three-dimensional biological dose distribution and biological dose volume histogram were displayed correctly by the Isobio software. Different physical doses were found between CERR and treatment planning system (TPS) in Oncentra, with 3.33% in high-risk clinical target volume (HR-CTV) determined by D 90% , 0.56% in the bladder, 1.74% in the rectum when determined by D 2cc , and less than 1% in Pinnacle. The difference in the EQD 2 between the software calculation and the manual calculation was not significantly different with 0.00% at p -values 0.820, 0.095, and 0.593 for external beam radiation therapy (EBRT) and 0.240, 0.320, and 0.849 for brachytherapy (BT) in HR-CTV, bladder, and rectum, respectively., Conclusions: The Isobio software is a feasible tool to generate the biological dose distribution and biological dose volume histogram for treatment plan evaluation in both EBRT and BT.

Cardiovascular complications are the most common cause of death among thalassemia patients in Thailand. In this study, we evaluated the prevalence of cardiac iron overload, cardiovascular complications and the associated risk factors. The information obtained will serve as a guidance for surveillance, prevention and early treatment of the complications. We conducted a cross sectional study of Thai patients with thalassemia attending Chiang Mai University Hospital, Thailand. Cardiac T2* magnetic resonance imaging (CMR T2*) was used to evaluate the myocardial iron deposition and echocardiography was used to evaluate the cardiac function and to identify pulmonary hypertension. Ninety-one patients were included in the study; 64% females with a median age of 31 (16-75) years. Of the total study subjects, 49% had homozygous β thalassemia, 32% had β thalassemia/Hb E disease, and 19% had Hb H disease. Half the participants were transfusion-dependent and 84% had received iron chelation. The CMR T2* showed cardiac iron overload in 10 patients (11%). The maximum ferritin level in the previous 3 years was higher among the patients with cardiac iron overload (6,310 ng/ml) than among the patients without cardiac iron overload (3,352 ng/ml) (p=0.001). Twenty-one patients (23%) had cardiovascular complications. Cardiomyopathy was seen in 8% of patients [17% in patients with transfusion-dependent thalassemia (TDT) and none in patients with non-transfusion-dependent thalassemia (NTDT)] and pulmonary hypertension in 15% of patients (14% in patients with TDT and 16% in patients with NTDT). TDT and cardiac iron overload were significantly associated with cardiomyopathy. No risk factors were found to be significantly associated with pulmonary hypertension. In summary, cardiac iron overload and cardiomyopathy are important complications in TDT while pulmonary hypertension is seen in both TDT and NTDT. Iron chelation and monitoring of serum ferritin level will prevent cardiac iron overload and cardiomyopathy. Interval monitoring with echocardiography will help with early identification of the cardiac complications.

Background: Iron overload cardiomyopathy remains the major cause of death in patients with transfusion-dependent thalassemia. Cardiac T2* magnetic resonance imaging is costly yet effective in detecting cardiac iron accumulation in the heart. Heart rate variability (HRV) has been used to evaluate cardiac autonomic function and is depressed in cases of thalassemia. We evaluated whether HRV could be used as an indicator for early identification of cardiac iron deposition., Methods: One hundred and one patients with transfusion-dependent thalassemia were enrolled in this study. The correlation between recorded HRV and hemoglobin, non-transferrin bound iron (NTBI), serum ferritin and cardiac T2* were evaluated., Results: The median age was 18 years (range 8-59 years). The patient group with a 5-year mean serum ferritin >5,000 ng/mL included significantly more homozygous β-thalassemia and splenectomized patients, had lower hemoglobin levels, and had more cardiac iron deposit than all other groups. Anemia strongly influenced all domains of HRV. After adjusting for anemia, neither serum ferritin nor NTBI impacted the HRV. However cardiac T2* was an independent predictor of HRV, even after adjusting for anemia. For receiver operative characteristic (ROC) curve analysis of cardiac T2* ≤20 ms, only mean ferritin in the last 12 months and the average of the standard deviation of all R-R intervals for all five-minute segments in the 24-hour recording were predictors for cardiac T2* ≤20 ms, with area under the ROC curve of 0.961 (p<0.0001) and 0.701 (p = 0.05), respectively., Conclusions: Hemoglobin and cardiac T2* as significant predictors for HRV indicate that anemia and cardiac iron deposition result in cardiac autonomic imbalance. The mean ferritin in the last 12 months could be useful as the best indicator for further evaluation of cardiac risk. The ability of serum ferritin to predict cardiac risk is stronger than observed in other thalassemia cohorts. HRV might be a stronger predictor of cardiac iron in study populations with lower somatic iron burdens and greater prevalence of cardiac iron deposition., Competing Interests: The authors have declared that no competing interests exist.

Short stature is one of the most common endocrinopathies in transfusion-dependent thalassemia (TDT). This study aimed to determine the longitudinal pattern of growth in pediatric patients with TDT and study the relationship between growth and hemoglobin level, serum ferritin level/iron overload parameters, and other clinical factors. The interval height-for-age Z-scores (HAZ) of 50 patients with TDT, of a mean age of 13.3±2.8 years, were analyzed using linear mixed model analysis. Nineteen patients (38%) had short stature with HAZ≤-2.0. The prevalence of short stature increased with age. The estimated mean HAZ decreased by 0.19 SD per year from the age of 5 years until approximately 14 years (95% confidence interval [CI], -0.22 to -0.16, P<0.001). Male sex (estimate, -0.28; 95% CI, -0.43 to -0.14; P<0.001), mean 3-year hemoglobin level ≤8 g/dL (estimate, -0.36; 95% CI, -0.53 to -0.19; P<0.001), mean 3-year ferritin level ≥1800 ng/mL (estimate, -0.44; 95% CI, -0.59 to -0.29; P<0.001), and cardiac T2* ≤20 ms (estimate, -1.05; 95% CI, -1.34 to -0.77; P<0.001) were significantly associated with short stature. In conclusion, short stature in patients with TDT is common and relates significantly with increasing age, male sex, hemoglobin level, and iron overload status.

Background and Objective: Heart failure due to iron-overload cardiomyopathy is one of the main causes of mortality. The cardiomyopathy is reversible if intensive iron chelation treatment is done in time, but the diagnosis is often delayed because the cardiac iron deposition is unpredictable and the symptoms are lately detected. There are many ways to assess iron-overload. However, the widely used and approved method is by using MRI which is performed by calculating the T2* (T2-star). In order to compute the T2* value, the region of interest (ROI) is manually selected by an expert which may require considerable time and skills. The aim of this work is hence to develop the cardiac T2* measurement by using region growing algorithm for automatically segmenting the ROI in cardiac MR images. Mathematical morphologies are also used to reduce some errors., Methods: Thirty MR images with free-breathing and respiratory-trigger technique were used in this work. The segmentation algorithm yields good results when compared with the manual segmentation performed by two experts., Results: The averages of positive predictive value, the sensitivity, the Hausdorff distance, and the Dice similarity coefficient are 0.76, 0.84, 7.78 pixels, and 0.80 when compared with the two experts' opinions. The T2* values were carried out based on the automatically segmented ROI's. The mean difference of T2* values between the proposed technique and the experts' opinion is about 1.40ms., Conclusions: The results demonstrate the accuracy of the proposed method in T2* value estimation. Some previous methods were implemented for comparisons. The results show that the proposed method yields better segmentation and T2* value estimation performances., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Iron overload cardiomyopathy remains the major cause of death in β-thalassemia (β-thal). Conventional routine screening parameters such as serum ferritin and echocardiogram (ECG) do not permit early detection of this condition. Although non-transferrin-bound iron (NTBI) is a reliable indicator for iron overload, it is still not universally available. Recently, heart rate variability (HRV), representing cardiac autonomic function, was found to be depressed in thalassemia patients. We hypothesized that HRV can be used for early detection of iron overload cardiomyopathy. Fifty patients (aged 29 ± 11 years; 31 females and 19 males) with β-thal were enrolled. The 24-hour Holter monitoring for HRV, serum ferritin, NTBI, hematological values and ECG were performed for each patient. Of the 50 patients, 29 carried β-thal major (β-TM). Non-transferrin-bound iron was weakly correlated to all time-domain HRV parameters. Low- and high-frequency domain HRV parameters were also inversely weakly correlated with NTBI. Neither HRV nor NTBI was correlated with serum ferritin. With its weak but significant correlation with NTBI, HRV may be considered to be used as a potential indicator of an iron overload condition and an early marker of cardiac involvement in patients with β-thal.

This article presents a small-flip-angle, three-dimensional tailored RF pulse that excites thin slices with an adjustable quadratic in-plane spatial variation. The quadratic spatial variation helps to compensate for the loss in image uniformity using a volume coil at 3 T due to the wavelike properties of the RF field. The pulse is based on a novel "fast-kz" design that uses a series of slice-select subpulses along kz and phase encoding "blips" along kx-ky. The method is demonstrated by acquiring a series of 5-mm-thick T2-weighted images of the human brain at 3 T using pulses 4.8 ms in length with a 45 degrees flip angle., ((c) 2006 Wiley-Liss, Inc.)

This work presents a small tip-angle 3D tailored RF slab-select pulse for reducing the B1 field inhomogeneity at 3T. The compensated slice profile was determined from a B1 inhomogeneity map. SNR improvement and degree of artifact reduction were evaluated in a NiCl2 doped phantom and human brains. The technique was found to reduce inhomogeneities as large as 30% of the peak image magnitude in all three spatial directions in the brain using a standard head coil.