Importance of gap evaluation in the ossification of posterior longitudinal ligament lesions using three-dimensional computed tomography.

BACKGROUND CONTEXT: Evaluating the gaps within the ossification of the posterior longitudinal ligament (OPLL) lesions, which may contribute to neurological symptoms, using conventional imaging techniques is challenging. OBJECTIVE: This study aimed to investigate the importance of evaluating gaps using three-dimensional computed tomography (3D-CT) and their association with the occurrence of magnetic resonance imaging (MRI) T2 high intensity in the spinal cord. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Retrospective analysis of 116 patients diagnosed with cervical OPLL. OUTCOME MEASURES: Presence of gaps in OPLL, presence of T2 high intensity in the cervical spinal cord, and OPLL thickness were evaluated. METHODS: Lateral X-ray, CT, and reconstructed 3D-CT images were reviewed to assess lesion characteristics and the presence of gaps. MRI was used to evaluate the change in spinal cord signal intensity. The relationship among gap presence, lesion morphology, and MRI T2 high intensity in the spinal cord was examined. RESULTS: A significant difference in gap detection accuracy was observed between CT and 3D-CT (p = 0.0054). CT demonstrated false-positive results in the detection of gaps as compared with 3D-CT. The presence of gaps was significantly associated with an increased likelihood of MRI T2 high intensity in the spinal cord (p = 0.037). Patients with thicker lesions and smaller space available for the spinal cord (SAC) were more likely to exhibit T2 high intensity. Meanwhile, patients with gaps co-occurring with T2 high intensity exhibited significantly thinner lesions (p = 0.011) and larger SACs (p = 0.0002). Patients with gaps had a significantly lower JOA scores (p = 0.0035), which indicates that patient with gaps are likely to exhibit more severe clinical neurological symptoms. CONCLUSION: 3D-CT showed superiority in accurately identifying gaps within OPLL lesions, while CT demonstrated false-positive results in the detection of gaps. Furthermore, the gap presence was a risk factor for MRI T2 high intensity in the spinal cord, independent of lesion thickness. In addition, gaps are related to more severe clinical symptoms. This study highlighted the importance of evaluating gaps within OPLL lesions using 3D-CT to clarify neurological pathogenesis.

Quantitative muscle magnetic resonance imaging in limb-girdle muscular dystrophy type R1 (LGMDR1): A prospective longitudinal cohort study.

Limb-girdle muscular dystrophy (LGMD) type R1 (LGMDR1) is the most common subtype of LGMD in Europe. Prospective longitudinal data, including clinical assessments and new biomarkers such as quantitative magnetic resonance imaging (qMRI), are needed to evaluate the natural course of the disease and therapeutic options. We evaluated eight thigh and seven leg muscles of 13 LGMDR1 patients (seven females, mean age 36.7 years, body mass index 23.9 kg/m2) and 13 healthy age- and gender-matched controls in a prospective longitudinal design over 1 year. Clinical assessment included testing for muscle strength with quick motor function measure (QMFM), gait analysis and patient questionnaires (neuromuscular symptom score, activity limitation [ACTIVLIM]). MRI scans were performed on a 3-T MRI scanner, including a Dixon-based sequence, T2 mapping and diffusion tensor imaging. The qMRI values of fat fraction (FF), water T2 relaxation time (T2), fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity were analysed. Within the clinical outcome measures, significant deterioration between baseline and follow-up was found for ACTIVLIM (p = 0.029), QMFM (p = 0.012). Analysis of qMRI parameters of the patient group revealed differences between time points for both FF and T2 when analysing all muscles (FF: p < 0.001; T2: p = 0.016). The highest increase of fat replacement was found in muscles with an FF of between 10% and 50% at baseline. T2 in muscles with low-fat replacement increased significantly. No significant differences were found for the diffusion metrics. Significant correlations between qMRI metrics and clinical assessments were found at baseline and follow-up, while only T2 changes in thigh muscles correlated with changes in ACTIVLIM over time (ρ = -0.621, p < 0.05). Clinical assessments can show deterioration of the general condition of LGMDR1 patients. qMRI measures can give additional information about underlying pathophysiology. Further research is needed to establish qMRI outcome measures for clinical trials.

Functional MRI assessment of the lungs in fetuses that deliver very Preterm: An MRI pilot study.

OBJECTIVES: To compare mean pulmonary T2* values and pulmonary volumes in fetuses that subsequently spontaneously delivered before 32 weeks with a control cohort with comparable gestational ages and to assess the value of mean pulmonary T2* as a predictor of preterm birth < 32 weeks' gestation. METHODS: MRI datasets scanned at similar gestational ages were selected from fetuses who spontaneously delivered < 32 weeks of gestation and a control group who subsequently delivered at term with no complications. All women underwent a fetal MRI on a 3 T MRI imaging system. Sequences included T2-weighted single shot fast spin echo and T2* sequences, using gradient echo single shot echo planar sequencing of the fetal thorax. Motion correction was performed using slice-to-volume reconstruction and T2* maps generated using in-house pipelines. Lungs were manually segmented and volumes and mean T2* values calculated for both lungs combined and left and right lung separately. Linear regression was used to compare values between the preterm and control cohorts accounting for the effects of gestation. Receiver operating curves were generated for mean T2* values and pulmonary volume as predictors of preterm birth < 32 weeks' gestation. RESULTS: Datasets from twenty-eight preterm and 74 control fetuses were suitable for analysis. MRI images were taken at similar fetal gestational ages (preterm cohort (mean ± SD) 24.9 ± 3.3 and control cohort (mean ± SD) 26.5 ± 3.0). Mean gestational age at delivery was 26.4 ± 3.3 for the preterm group and 39.9 ± 1.3 for the control group. Mean pulmonary T2* values remained constant with increasing gestational age while pulmonary volumes increased. Both T2* and pulmonary volumes were lower in the preterm group than in the control group for all parameters (both combined, left, and right lung (p < 0.001 in all cases). Adjusted for gestational age, pulmonary volumes and mean T2* values were good predictors of premature delivery in fetuses < 32 weeks (area under the curve of 0.828 and 0.754 respectively). CONCLUSION: These findings indicate that mean pulmonary T2* values and volumes were lower in fetuses that subsequently delivered very preterm. This may suggest potentially altered oxygenation and indicate that pulmonary morbidity associated with prematurity has an antenatal antecedent. Future work should explore these results correlating antenatal findings with long term pulmonary outcomes.

Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Presenting During the Postpartum Period as Postpartum Depression and Postpartum Psychosis.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited disease that presents with neurologic manifestations such as stroke, psychiatric disturbances, migraine, and cognitive decline. We report a case of a previously well 27-year-old lady presenting with new onset confusion four weeks postpartum. On examination, there was right-sided weakness and tremors. A thorough history revealed existing diagnoses of CADASIL in 1st and 2nd-degree relatives. The diagnosis in this patient was confirmed by MRI of the brain and genetic testing for NOTCH 3 mutation. The patient was admitted to the stroke ward, treated with a single antiplatelet agent for stroke, and supported by speech and language therapy. There was a significant symptomatic improvement in her speech at the time of discharge. The mainstay of treatment for CADASIL remains symptomatic at this stage. This case report shows that the first presentation of CADASIL can mimic postpartum psychiatric disorders in a puerperal woman.

No difference in myocardial iron concentration and serum ferritin with deferasirox and deferiprone in pediatric patients with hemoglobinopathies: A systematic review and meta-analysis.

OBJECTIVES: Iron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP) are effective in overcoming this problem. We conducted this systematic review and meta-analysis to evaluate the effectiveness of DFX compared to DFP in treating iron overload amongst pediatric patients with hemoglobin disorders. MATERIAL AND METHODS: PubMed and Cochrane Central were searched from their inception until Dec 21 2021, for randomized clinical trials (RCTs) and observational studies, which assessed the efficacy of DFX compared to DFP in the treatment of inherited hemoglobin disorders. The outcomes of interest included myocardial iron concentration (MRI T2*) at the end of the trial and change in mean serum ferritin (SF) levels at the 6 and 12 months mark. Weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were calculated for continuous outcomes using random effects model. RESULTS: A total of 5 studies comprising 607 children were included. The results of our analysis revealed no significant difference between DFX and DFP in MRI T2* at the end of treatment (WMD: -0.92; 95% CI [-3.35, 1.52]; p = 0.46; I2 = 0). Moreover, there has been no significant difference noted in SF levels at both 6 months (WMD: 97.31; 95% CI [-236.16, 430.77]; p = 0.57; I2 = 0) and 12 months (WMD: 46.99; 95% CI [-191.42, 285.40]; p = 0.70; I2 = 0) respectively. CONCLUSION: Our analysis shows no significant difference between the efficacy of DFX and DFP in the management of iron overload in children with inherited blood disorders. Future large-scale clinical trials are required to further validate our results.

The role of MRI-R2* in the detection of subclinical pancreatic iron loading among transfusion-dependent sickle cell disease patients and correlation with hepatic and cardiac iron loading.

OBJECTIVES: Pancreatic reserve could be preserved by early assessment of pancreatic iron overload among transfusion-dependent sickle cell disease (SCD) patients. This study aimed to measure pancreatic iron load and correlate its value with patients' laboratory and radiological markers of iron overload. MATERIALS AND METHODS: Sixty-six SCD children and young adults underwent MRI T2* relaxometry using a simple mathematical spreadsheet and laboratory assessment. RESULTS: The results indicated moderate-to-severe hepatic iron overload among 65.2% of studied cases. None had cardiac iron overload. Normal-to-mild iron overload was present in the pancreas in 86% of cases, and 50% had elevated serum ferritin > 2500 ug/L. There was no significant correlation between pancreatic R2* level, serum ferritin, and hepatic iron overload. Patients with higher levels of hemolysis markers and lower pre-transfusion hemoglobin levels showed moderate-to-severe pancreatic iron overload. CONCLUSION: Chronically transfused patients with SCD have a high frequency of iron overload complications including pancreatic iron deposition, thereby necessitating proper monitoring of the body's overall iron balance as well as detection of extrahepatic iron depositions.

Two trade names of deferasirox (Osveral® and Exjade®) in reduction of iron overload parameters in major beta-thalassemia patients: A randomized open labeled clinical trial.

BACKGROUND: Beta-thalassemia major patients typically require chronic transfusion and iron-chelating agents to reduce serum iron overload. Osveral® is an available Iranian brand name of deferasirox used by majority of thalassemic patients. The aim of this study was to compare the efficacy of Osveral® vs. Exjade® in major beta- thalassemia patients. METHODS: In this randomized clinical trial, all patients received a single daily dose of 30 mg/kg either of Osveral® or Exjade® for 6 months. Primary outcome was the mean of bimonthly changes in serum ferritin concentration and secondary outcomes included mean changes of heart and liver MRI T2* after a year. RESULTS: Finally, 80 patients completed the study. The mean serum ferritin level at the end of sixth month significantly decreased in Osveral® and Exjade® groups (p<0.01). After a year, means cardiac MRI T2* in Osveral® group were changed from 25.9±9.6 ms to 25.4±9.7 ms and in Exjade® group from 24.8±9.2 ms to 26.9±5.9 ms, with no significant difference (P=0.43). Mean liver MRI T2* for Osveral® and Exjade® groups were 8.6±6.4 ms (baseline 6.3±4.7) and 6.3±4 ms (baseline 4.9±3.5), respectively and there was no significant difference between two study arms (P=0.1). CONCLUSION: Osveral® decreased significantly the serum ferritin level and improved heart and liver iron overload as efficient as Exjade®. It can be a suitable cost-effective alternative agent in beta-thalassemia major patients.

Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2.

Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO2 ). Cardiac T2 is sensitive to these changes and therefore is a promising non-contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14-0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2 = 37.6-41.8 ms; MBF = 0.48-1.32 mL/min/g; RPP = 6507-4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant ß-values >7). Myocardial oxygen consumption had almost no effect on T2 (ß-values <0.002); since PvO2 is influenced by both oxygen consumption and MBF, PvO2 changes detected by T2 during adenosine stress can be attributed to MBF. Simulations varying PvO2 and MBV confirmed that PvO2 had the strongest influence on T2, but MBV became important at high PvO2 . Together, these data suggest a model where, during adenosine stress, myocardial T2 responds predominantly to changes in MBF, but at high hyperemia MBV is also influential. Thus, changes in adenosine stress T2 can now be interpreted in terms of the physiological changes that led to it, enabling T2 mapping to become a viable non-contrast option to detect ischemic myocardial tissue.

Magnetic resonance imaging T2* of the pancreas value using an online software tool and correlate with T2* value of myocardium and liver among patients with transfusion-dependent thalassemia major.

Objective: Patients with thalassemia major do require lifetime blood transfusions that eventually result in iron accumulation in different organs. We described the usefulness of using magnetic resonance imaging (MRI) T2*imaging values for the evaluation of pancreatic iron load in these patients, and we correlated it with MRI T2* haemosiderosis of the myocardium and liver that has been recognized as a non-invasive assessment of iron overload among patients with thalassemia major. Materials and methods: We conducted a cross-sectional study on 39 patients with thalassemia major in one of the tertiary university hospitals for a 1-year period. Demographic data were collected from the patient's history. MRI T2* of the pancreas, liver, and heart were executed on all patients in the same setting. Objective values of iron overload in these organs were obtained using the MRI post-processing software from online software. Results: A total of 32 (82.1%) patients had pancreatic iron overload including 2 patients (5.1%) with severe iron overload and 15 patients (38.5%) with moderate and mild iron overload, respectively. Nine patients (23.1%) had myocardial iron overload, which included 3 patients (7.7%) who had severe cardiac haemosiderosis. Notably, 37 patients (94.9%) had liver iron overload, which included 15 patients (38.5%) who had severe liver haemosiderosis. There was a moderate positive correlation between the relaxation time of the pancreas and heart haemosiderosis (r = 0.504, P < 0.001). No significant correlation was found between the relaxation time of the pancreas with the liver and the heart with the liver. Conclusion: Pancreatic haemosiderosis precedes cardiac haemosiderosis, which establishes a basis for initiating earlier iron chelation therapy to patients with thalassemia major.

Correlation of Serum Ferritin and Cardiac Iron Toxicity with Cardiac Function in Transfusion Dependent Beta-Thalassemia Major Patients.

BACKGROUND: Cardiac iron toxicity is a major cause of mortality in transfusion-dependent beta-thalassemia major patients. The main modality for detecting cardiac iron toxicity is MRI T2* with limited availability. This study aims to obtain iron toxicity profiles in transfusion-dependent beta-thalassemia patients; to see a correlation between iron toxicity and cardiac function. METHODS: We conducted a cross-sectional study at the Adult Thalassemia Polyclinic of Cipto Mangunkusumo Hospital, Indonesia from December 2017 to March 2018. We performed the statistical analysis using Pearson/Spearman Test comparing MRI T2* values with ejection fraction and E/A ratio. RESULTS: The median of 4-months mean of ferritin levels was 5130 ng/mL. The mean for cardiac T2* was 24.96 ms. Severe cardiac hemosiderosis (mean cardiac MRI T2* < 10 ms)  occurred in 11.3% of the subjects.  There was weak correlation between serum ferritin with cardiac iron toxicity (r=-0.272, p=0.032) and ejection fraction (r=-0.281, p=0.013). But, there was no correlation between cardiac iron toxicity with ejection fraction and E/A ratio. CONCLUSION: Serum ferritin correlated weakly with cardiac iron toxicity and cardiac systolic function. Meanwhile, there was no correlation between cardiac iron toxicity with cardiac systolic and diastolic function.

Correlation of Serum Ferritin and Liver Iron Concentration with Transient Liver Elastography in Adult Thalassemia Intermedia Patients with Blood Transfusion.

INTRODUCTION: Iron overload is a common feature of thalassemia intermedia due to regular blood transfusion and increased gastrointestinal iron absorption. Early detection and adequate iron chelator can decrease morbidity and mortality from iron overload. Liver iron concentration (LIC) by MRI T2* is the best non-invasive way to measure body iron stores. However, this method is expensive and not available nationwide in Indonesia. The aim of this study was to identify liver iron overload and correlation of transferrin saturation, serum ferritin, liver MRI T2* and LIC with transient liver elastography in adult thalassemia intermedia patients. METHODS: This is a cross-sectional study of 45 patients with thalassemia intermedia with blood transfusion and with and without iron chelator therapy. The study was conducted at Cipto Mangunkusumo Hospital from August through October 2016. We performed measurements of transferrin saturation, serum ferritin level, transient liver elastography and liver MRI T2*. Pearson and Spearman correlation tests were used to evaluate the correlation between transient liver elastography with transferrin saturation, serum ferritin, liver MRI T2*and LIC. RESULTS AND DISCUSSION: This study showed that 64.4% of study subjects are ß-Hb E thalassemia intermedia. Furthermore, 84.4% of study subjects have regular transfusion. Based on liver MRI T2*all subjects suffered from liver iron overload, 48.9% had severe degree. Median value of liver MRI T2* was 1.6 ms. Mean serum ferritin was 2831 ng/mL, with median transferrin saturation of 66%. Mean of LIC corresponding to liver MRI T2* and mean liver stiffness measurement was 15.36±7.37 mg Fe/gr dry weight and 7.7±3.8 kPa, respectively. Liver stiffness correlated with serum ferritin (r=0.651; p=0.000), liver MRI T2* (r=-0.357; p=0.016), and LIC (r=0.433; p=0.003). No correlation was found between liver elastography and transferrin saturation (r=0.204; p=0.178). CONCLUSION: Serum ferritin, liver MRI T2*and LIC correlated with liver elastography. No correlation was found between transferrin saturation and liver elastography.

Visualizing pre-osteoarthritis: Integrating MRI UTE-T2* with mechanics and biology to combat osteoarthritis-The 2019 Elizabeth Winston Lanier Kappa Delta Award.

Osteoarthritis (OA) is a leading cause of pain and disability for which disease-modifying treatments remain lacking. This is because the symptoms and radiographic changes of OA occur after the onset of likely irreversible changes. Defining and treating earlier disease states are therefore needed to delay or to halt OA progression. Taking this concept a step further, studying OA pathogenesis before disease onset by characterizing potentially reversible markers of increased OA risk to identify a state of "pre-osteoarthritis (pre-OA)" shifts the paradigm towards OA prevention. The purpose of this review is to summarize the 42 studies comprising the 2019 Kappa Delta Elizabeth Lanier Award where conceptualization of a systems-based definition for "pre-osteoarthritis (pre-OA)" was followed by demonstration of potentially reversible markers of heightened OA risk in patients after anterior cruciate ligament (ACL) injury and reconstruction. In the process, these efforts contributed a new magnetic resonance imaging method of ultrashort echo time (UTE) enhanced T2* mapping to visualize joint tissue damage before the development of irreversible changes. The studies presented here support a transformative approach to OA that accounts for interactions between mechanical, biological, and structural markers of OA risk to develop and evaluate new treatment strategies that can delay or prevent the onset of clinical disease. This body of work was inspired by and performed for patients. Shifting the paradigm from attempting to modify symptomatic radiographic OA towards monitoring and reversing markers of "pre-OA" opens the door for transforming the clinical approach to OA from palliation to prevention.

Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

Reduction of Liver Iron Load in Adult Patients with ß-Thalassemia Major Treated with Modern Chelation Modalities.

BACKGROUND: Management of beta-thalassemia major (TM) requires life-long hemotransfusions leading to iron overload. Iron elimination is enhanced by the use of modern chelators. AIM: To assess the effect of modern chelation therapy by dynamics of serum ferritin concentration and liver MRI T2*. PATIENTS AND METHODS: Forty-six patients with TM (male to female ratio =1:1, mean age 33.2±10.9 years) were prospectively studied between 2011 and 2014. Twenty-one patients (45.7%) were treated with deferasirox, 17 (37%) - with deferiprone, and 8 (17.3%) - with deferiprone in combination with deferoxamine. Ferritin was measured by ELISA. MRI T2* was assessed by Siemens Magnetom Avanto 1.5T. The patients were allocated into 3 groups based on their initial ferritin level and liver MRI T2*. Statistical analysis was performed using SPSS v. 18 for Windows. Data were analysed by descriptive analysis, analysis of variance and correlative analysis, means were compared using t-test and one-way ANOVA. RESULTS: In 2011, 9 (19.5%) patients had normal liver MRI T2*; in 2014 they were 17 (37%). The patients with mild grade liver siderosis were 12 (26%) in 2011, and in 2014 they were 14 (30.4%). In 2011, the patients with moderate liver siderosis were 14 (30.4%), and in 2014 - 12 (26.0%). Eleven patients (23.9%) had severe liver siderosis in 2011 and only two patients (4.0%) were diagnosed with the condition in 2014. CONCLUSION: A reduction of iron overload was found in all studied groups. This positive effect is attributed to the use of modern chelators and the ease of access to accurate monitoring.

Cardiac T2* MR in patients with thalassemia major: a 10-year long-term follow-up.

The consequence of regular blood transfusion in patients with thalassemia major (TM) is iron overload. Herein, we report the long-term impact of chelation on liver iron concentration (LIC) and cardiac T2* MR in patients with TM. This is a retrospective cohort study over 10 years of adolescents and adults with TM aged at least 10 years who had their first cardiac T2* MR between September 2006 and February 2007. One-year chelation therapy was considered the unit of analysis. A total of 99 patients were included in this study with a median age of 18 years. The median cardiac T2* MR and LIC at baseline were 19 ms and 11.6 mg/g dw, respectively. During follow-up, 18 patients died and six underwent successful bone marrow transplantation. Factors associated with decreased survival were older age (HR 1.12, p = 0.014) and high risk cardiac T2* (HR 8.04, p = 0.004). The median cardiac T2* and LIC significantly improved over the 10-year follow-up period (p = 0.000011 and 0.00072, respectively). In conclusion, this long-term "real-life" study confirms that low cardiac T2* adversely impacts the overall survival in patients with TM. Higher baseline LIC predicts a larger reduction in LIC, and lower baseline cardiac T2* predicts a larger improvement in T2*.

The corrected QT interval prolongation in adolescents with cardiac iron overload ß-thalassemia major.

BACKGROUND AND OBJECTIVES: Iron-induced cardiomyopathy remains the leading cause of mortality in ß-thalassemia major patients. The T2* magnetic resonance imaging (MRI) technique is the gold standard for iron load detection, yet it is expensive and not widely available especially in the developing countries. Some previous studies showed that QTc interval could be used as an early detection of cardiac iron overload. This study aimed to evaluate the diagnostic value of QTc interval as a marker of early detection of cardiac iron overload in adolescent beta thalassemia major patients. METHODS: We prospectively evaluated electrocardiography (ECG) parameter of QTc interval in 50 ß-thalassemia major patients aged 10-18 years. All participants had a 12-lead ECG evaluation, echocardiogram and cardiac MRI T2* examination within three months (average 15 days). They were categorized as cardiac iron overload (MRI T2* < 20 millisecond) and non-cardiac iron overload (MRI T2* > 20 millisecond). RESULTS: Of the 50 patients, the male to female ratio was 1.08:1 and the mean age was 13.7 ± 2.43 years. All participants showed normal systolic and diastolic function using conventional echocardiography. The mean QTc interval was significantly different between cardiac iron overload group (464.44 ± 20.35 ms) and noncardiac iron overload group (431.09 ± 32.29) (p= 0.001). Diagnostic study of QTc interval resulted in AUC 0.8 (p= 0.002). Calculated sensitivity and specificity of QTc interval were 0.88 and 0.73 respectively, with cut-off point of 449 ms. CONCLUSION: Cardiac iron overload is associated with QTc prolongation in adolescents. QTc interval of 449 ms could be considered as a cut-off point of cardiac iron overload.

Diffusion weighted imaging improves diagnostic ability of MRI for determining complete response to neoadjuvant therapy in locally advanced rectal cancer.

PURPOSE: To assess the diagnostic performance, interobserver agreement and confidence level for determining response to neoadjuvant chemoradiotherapy (NACRT) using morphology based MR-tumour regression grade (MR TRG), diffusion weighted imaging (DWI) patterns and their combination in patients with locally advanced rectal cancer. METHODS: This was a retrospective study including patients with locally advanced rectal cancer treated with NACRT and subsequent surgery. Two independent radiologists blinded to the histopathology reviewed staging and restaging MRI. Diagnostic performance of morphology based MR-TRG, DWI patterns and their combination for determining complete (CR) and incomplete (IR) response was assessed with pathological response as the reference. Likert's scale was used to assess the radiologist's level of confidence. Interobserver agreement was determined using Kappa statistics. RESULTS: The study included 251 patients (mean age of 47.9+/-14 (range 19-86) years, M:F = 164:87). Rate of pathological CR was 14.7 % (n = 37). Pattern based interpretation of DWI and combined approach (DWI + T2-HR) had superior diagnostic performance than morphology based assessment alone with area under curve (AUC) for T2HR, DWI and their combination being 0.531, 0.887, 0.874 respectively for observer 1 and 0.558, 0.653, 0.678 respectively for observer 2, p < 0.001. Interobserver agreement was substantial (k = 0.688) for combined approach, moderate (k = 0.402) for DWI patterns and fair (k = 0.265) for T2 HR MRI with both observers exhibiting highest level of confidence for determining response with the combined approach. CONCLUSION: Complete response to neoadjuvant chemoradiotherapy can be determined with excellent accuracy, substantial interobserver agreement and high level of confidence by combined interpretation of DWI and T2 high resolution MRI.

Global longitudinal strain as an Indicator of cardiac Iron overload in thalassemia patients.

BACKGROUND AND OBJECTIVE: Cardiac involvement due to iron overload is the most common cause of morbidity and mortality in patients with thalassemia, and many patients remain asymptomatic until the late stages. Therefore, early detection of heart problems in such patients at subclinical stages can improve the prognosis of these patients. We investigated the role of speckled tracking (SI) and tissue Doppler echocardiography (TDI) in early detection of iron overload in these patients. METHODS: 52 thalassemic patients who were receiving regular blood transfusion with normal global LV function were examined by two- and three-dimensional echocardiography. Cardiac MRI was done and T2* images were considered as the non-invasive gold standard for evaluating cardiac iron deposition. Serum ferritin level was assessed and the relationships between serum ferritin levels and echo finding with cardiac MRI T2* was investigated. RESULTS: No significant relationship was seen between serum ferritin levels and cardiac MRI T2*. Among the echocardiographic findings, septal systolic myocardial velocity (P = 0.002 and r = 0.43) and global strain (GLS) (P = 0.000 and r = 0.60) were significantly associated with T2*. A GLS < 19.5 could predict a T2* level below 20 by 82.14% sensitivity and 86.36% specificity (area under the curve = 0.87; p < 0.0001). CONCLUSION: While serum ferritin level and ejection fraction are not useful candidates, GLS may be used as a valuable marker to screen thalassemia patients for myocardial iron deposition, using a cut off value below - 19.5. This approach may facilitate the cardiac follow up, reduce the costs, and contribute to preventing deterioration of cardiac function in countries with limited availability of cardiac MRI.

Quantitative MRI UTE-T2* and T2* Show Progressive and Continued Graft Maturation Over 2 Years in Human Patients After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Noninvasive quantitative magnetic resonance imaging (MRI) measures to assess anterior cruciate ligament (ACL) graft maturity are needed to help inform return to high-demand activities and to evaluate the effectiveness of new treatments to accelerate ACL graft maturation. Quantitative MRI ultrashort echo time T2* (UTE-T2*) and T2* mapping captures short T2 signals arising from collagen-associated water in dense regular connective tissues, such as tendon, ligament, and maturing grafts, which are invisible to conventional MRI. HYPOTHESIS: Quantitative MRI UTE-T2* and T2* mapping is sensitive to ACL graft changes over the first 2 years after ACL reconstruction (ACLR). STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 32 patients (18 men; mean ± SD age, 30 ± 9 years) undergoing unilateral ACLR and 30 uninjured age-matched controls (18 men; age, 30 ± 9 years) underwent 3-T MRI examination. Patients who underwent ACLR were imaged at 6 weeks, 6 months, and 1 and 2 years postoperatively. Two separate ACLR cohorts were scanned with 2 MRI platforms at 2 institutions. Twelve ACLR knees were scanned with a 3-dimensional acquisition-weighted stack of spirals UTE sequence on a Siemens scanner, and 20 ACLR knees were scanned with a 3-dimensional Cones UTE sequence on a GE scanner. UTE-T2* or T2* maps were calculated for the intra-articular portion of the ACL graft. RESULTS: Mean ACL graft UTE-T2* and T2* decreased from 1 to 2 years after ACLR. ACL graft T2* increased 25% to 30% during the first 6 months (P < .013) to a level not different from that of uninjured native ACL (P > .4), stabilized between 6 months and 1 year (P ≥ .999), and then decreased 19% between 1 and 2 years after ACLR (P = .027). At 6-month follow-up, ACL graft UTE-T2* differed from that of tendon (P < .02) but not uninjured native ACL (P > .7) and showed the greatest variability among patients. CONCLUSION: UTE-T2* mapping suggested substantial changes within the graft during the first 6 months postsurgery. T2* and UTE-T2* mapping showed relatively stable graft composition from 6 months to 1 year, consistent with remodeling, followed by decreases from 1 to 2 years, suggestive of continuing maturation. MRI UTE-T2* and T2* mapping demonstrated potential clinical utility as noninvasive quantitative imaging metrics for evaluation of human ACL grafts.

Effect of diminished flow in rabbit lumbar arteries on intervertebral disc matrix changes using MRI T2-mapping and histology.

BACKGROUND: Impaired lumbar artery flow has been reported in clinical and epidemiological studies to be associated with low back pain and lumbar disc degeneration. However, it has not been experimentally demonstrated that impaired lumbar artery flow directly induces intervertebral disc (IVD) degeneration by affecting IVD matrix metabolism. The purpose of this study was to evaluate whether ligation of the lumbar artery can affect degenerative changes in the rabbit IVD. METHODS: New Zealand White rabbits (n = 20) were used in this study. Under general anesthesia, the third and fourth lumbar arteries were double-ligated using vascular clips. The blood flow to the L3/L4 disc (cranial disc) was reduced by ligation of the third lumbar artery and that of the L5/L6 disc (caudal disc) by ligation of the fourth lumbar artery. The blood flow to the L4/L5 disc (bilateral disc) was decreased by ligation of both the third and fourth lumbar arteries. The L2/L3 disc was used as the control. Disc height was radiographically monitored biweekly until 12 weeks after surgery. The rabbits were sacrificed at 4, 8, and 12 weeks after surgery and magnetic resonance imaging (MRI) T2-mapping, histology and immunohistochemistry were assessed. RESULTS: Lumbar artery ligation did not induce significant changes in disc height between control and ischemic discs (cranial, bilateral and caudal discs) during the 12-week experimental period. T2-values of ischemic discs had no significant trend to be lower than those of the control L2/L3 discs. Histologically, Safranin-O staining changed following ligation of corresponding IVD lumbar arteries. Histological grading scores for disc degeneration, which correlated significantly with MRI T2-values, had significant changes after the surgery. Immunohistochemical analysis showed that the ligation of lumbar arteries significantly affected a change in the percentage of HIF-1α immunoreactive cells of ischemia discs compared to that of control discs four weeks after the surgery (p < 0.05). CONCLUSIONS: The MRI and histology results suggest that diminished flow in lumbar arteries induce mild changes in the extracellular matrix metabolism of rabbit IVDs. These matrix changes, however, were not progressive and differed from the degenerative disc changes seen in the process of human IVD degeneration.