An Improved Postprocessing Method to Mitigate the Macroscopic Cross-Slice B0 Field Effect on R2* Measurements in the Mouse Brain at 7T.

The MR transverse relaxation rate, R2*, has been widely used to detect iron and myelin content in tissue. However, it is also sensitive to macroscopic B0 inhomogeneities. One approach to correct for the B0 effect is to fit gradient-echo signals with the three-parameter model, a sinc function-weighted monoexponential decay. However, such three-parameter models are subject to increased noise sensitivity. To address this issue, this study presents a two-stage fitting procedure based on the three-parameter model to mitigate the B0 effect and reduce the noise sensitivity of R2* measurement in the mouse brain at 7T. MRI scans were performed on eight healthy mice. The gradient-echo signals were fitted with the two-stage fitting procedure to generate R2corr_t*. The signals were also fitted with the monoexponential and three-parameter models to generate R2nocorr* and R2corr*, respectively. Regions of interest (ROIs), including the corpus callosum, internal capsule, somatosensory cortex, caudo-putamen, thalamus, and lateral ventricle, were selected to evaluate the within-ROI mean and standard deviation (SD) of the R2* measurements. The results showed that the Akaike information criterion of the monoexponential model was significantly reduced by using the three-parameter model in the selected ROIs (p = 0.0039-0.0078). However, the within-ROI SD of R2corr* using the three-parameter model was significantly higher than that of the R2nocorr* in the internal capsule, caudo-putamen, and thalamus regions (p = 0.0039), a consequence partially due to the increased noise sensitivity of the three-parameter model. With the two-stage fitting procedure, the within-ROI SD of R2corr* was significantly reduced by 7.7-30.2% in all ROIs, except for the somatosensory cortex region with a fast in-plane variation of the B0 gradient field (p = 0.0039-0.0078). These results support the utilization of the two-stage fitting procedure to mitigate the B0 effect and reduce noise sensitivity for R2* measurement in the mouse brain.

Brain structural and functional abnormalities associated with acute post-traumatic headache: iron deposition and functional connectivity.

BACKGROUND: The purpose of this study was to interrogate brain iron accumulation in participants with acute post-traumatic headache (PTH) due to mild traumatic brain injury (mTBI), and to determine if functional connectivity is affected in areas with iron accumulation. We aimed to examine the correlations between iron accumulation and headache frequency, post-concussion symptom severity, number of mTBIs, and time since most recent TBI. METHODS: Sixty participants with acute PTH and 60 age-matched healthy controls (HC) underwent 3T magnetic resonance imaging including quantitative T2* maps and resting-state functional connectivity imaging. Between group T2* differences were determined using T-tests (p < 0.005, cluster size threshold of 90 voxels). For regions with T2* differences, two analyses were conducted. First, the correlations with clinical variables including headache frequency, number of lifetime mTBIs, time since most recent mTBI, and Sport Concussion Assessment Tool (SCAT) symptom severity scale scores were investigated using linear regression. Second, the functional connectivity of these regions with the rest of the brain was examined (significance of p < 0.05 with family wise error correction for multiple comparisons). RESULTS: The acute PTH group consisted of 60 participants (22 male, 38 female) with average age of 42 ± 14 years. The HC group consisted of 60 age-matched controls (17 male, 43 female, average age of 42 ± 13). PTH participants had lower T2* values compared to HC in the left posterior cingulate and the bilateral cuneus. Stronger functional connectivity was observed between bilateral cuneus and right cerebellar areas in PTH compared to HC. Within the PTH group, linear regression showed negative associations of T2* in the left posterior cingulate with SCAT symptom severity score (p = 0.05) and T2* in the left cuneus with headache frequency (p = 0.04). CONCLUSIONS: Iron accumulation in posterior cingulate and cuneus was observed in those with acute PTH relative to HC; stronger functional connectivity was detected between the bilateral cuneus and the right cerebellum. The correlations of decreased T2* (suggesting higher iron content) with headache frequency and post mTBI symptom severity suggest that the iron accumulation that results from mTBI might reflect the severity of underlying mTBI pathophysiology and associate with post-mTBI symptom severity including PTH.

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.

Value of speckle tracking echocardiography for detection of clinically silent left ventricular dysfunction in patients with ß-thalassemia.

OBJECTIVE: ß-Thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia requiring chronic transfusion therapy. Cardiac involvement is the main cause of death in patients with thalassemia major. The narrow border is between overt myocardial dysfunction and clinically silent left ventricular (LV) dysfunction in patients with thalassemia. Therefore, we need novel parameters in different imaging techniques to discover cardiac involvement in an early and subtle stage. We explore to find a novel, straightforward and informative parameter in echocardiography as a noninvasive, economical and really routine in clinical practice. METHODS: In this prospective study, 55 patients, who are known cases of ß-thalassemia major, receiving long-term blood transfusions and undergoing iron chelation therapy were enrolled. Ferritin level, cardiac magnetic resonance (CMR) T2 * value, full conventional echocardiography and speckle tracking, LV regional circumferential and longitudinal strain values (%) and time-to-peak strain (ms) of 17 segments cardiac model in eyeball tomogram were measured. RESULTS: There was a significant reduction in global longitudinal strain (GLS) (-20.9% ± 1.9 vs. -22.2 ± 1.03) and also basal segments longitudinal strain compared to normal subjects group (-17.4% ± 2.7 vs. -19.6% ± 1.2). There was no significant difference in circumferential strain value between thalassemia patients and normal control group. Interestingly, there was no significant correlation between GLS and CMR T2 * values showing no association between cardiac iron load and longitudinal strain. CONCLUSION: Speckle tracking echocardiography could be used as a feasible method for evaluating subclinical myocardial dysfunction in patients with thalassemia major. Echocardiography, using GLS, could predict clinically silent myocardial dysfunction independent of CMR (T2 * value) and extension of iron deposition. Our study also puts forward other causes such as chronic tissue hypoxia resulting from chronic anemia as a root cause and initiating factor for subsequent injury by the iron deposition. Speckle tracking can recognize the cardiac involvement in really early stages.

Feasibility of in vivo three-dimensional T 2* mapping using dicarboxy-PROXYL and CW-EPR-based single-point imaging.

OBJECTIVES: The aim of this study was to demonstrate the feasibility of in vivo three-dimensional (3D) relaxation time T 2* mapping of a dicarboxy-PROXYL radical using continuous-wave electron paramagnetic resonance (CW-EPR) imaging. MATERIALS AND METHODS: Isotopically substituted dicarboxy-PROXYL radicals, 3,4-dicarboxy-2,2,5,5-tetra(2H3)methylpyrrolidin-(3,4-2H2)-(1-15N)-1-oxyl (2H,15N-DCP) and 3,4-dicarboxy-2,2,5,5-tetra(2H3)methylpyrrolidin-(3,4-2H2)-1-oxyl (2H-DCP), were used in the study. A clonogenic cell survival assay was performed with the 2H-DCP radical using squamous cell carcinoma (SCC VII) cells. The time course of EPR signal intensities of intravenously injected 2H,15N-DCP and 2H-DCP radicals were determined in tumor-bearing hind legs of mice (C3H/HeJ, male, n = 5). CW-EPR-based single-point imaging (SPI) was performed for 3D T 2* mapping. RESULTS: 2H-DCP radical did not exhibit cytotoxicity at concentrations below 10 mM. The in vivo half-life of 2H,15N-DCP in tumor tissues was 24.7 ± 2.9 min (mean ± standard deviation [SD], n = 5). The in vivo time course of the EPR signal intensity of the 2H,15N-DCP radical showed a plateau of 10.2 ± 1.2 min (mean ± SD) where the EPR signal intensity remained at more than 90% of the maximum intensity. During the plateau, in vivo 3D T 2* maps with 2H,15N-DCP were obtained from tumor-bearing hind legs, with a total acquisition time of 7.5 min. CONCLUSION: EPR signals of 2H,15N-DCP persisted long enough after bolus intravenous injection to conduct in vivo 3D T 2* mapping with CW-EPR-based SPI.