Distribution of Silent Cerebral Infarcts in Adults With Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: Previously we demonstrated that 90% of infarcts in children with sickle cell anemia occur in the border zone regions of cerebral blood flow (CBF). We tested the hypothesis that adults with sickle cell disease (SCD) have silent cerebral infarcts (SCIs) in the border zone regions, with a secondary hypothesis that older age and traditional stroke risk factors would be associated with infarct occurrence in regions outside the border zones. METHODS: Adults with SCD 18-50 years of age were enrolled in a cross-sectional study at 2 centers and completed a 3T brain MRI. Participants with a history of overt stroke were excluded. Infarct masks were manually delineated on T2-fluid-attenuated inversion-recovery MRI and registered to the Montreal Neurological Institute 152 brain atlas to generate an infarct heatmap. Border zone regions between anterior, middle, and posterior cerebral arteries (ACA, MCA, and PCA) were quantified using the Digital 3D Brain MRI Arterial Territories Atlas, and logistic regression was applied to identify relationships between infarct distribution, demographics, and stroke risk factors. RESULTS: Of 113 participants with SCD (median age 26.1 years, interquartile range [IQR] 21.6-31.4 years, 51% male), 56 (49.6%) had SCIs. Participants had a median of 5.5 infarcts (IQR 3.2-13.8). Analysis of infarct distribution showed that 350 of 644 infarcts (54.3%) were in 4 border zones of CBF and 294 (45.6%) were in non-border zone territories. More than 90% of infarcts were in 3 regions: the non-border zone ACA and MCA territories and the ACA-MCA border zone. Logistic regression showed that older participants have an increased chance of infarcts in the MCA territory (odds ratio [OR] 1.08; 95% CI 1.03-1.13; p = 0.001) and a decreased chance of infarcts in the ACA-MCA border zone (OR 0.94; 95% CI 0.90-0.97; p < 0.001). The presence of at least 1 stroke risk factor did not predict SCI location in any model. DISCUSSION: When compared with children with SCD, in adults with SCD, older age is associated with expanded zones of tissue infarction that stretch beyond the traditional border zones of CBF, with more than 45% of infarcts in non-border zone regions.

In vivo lymph node CEST-Dixon MRI in breast cancer patients with metastatic lymph node involvement.

PURPOSE: Axillary lymph nodes (LNs) often present a reservoir for metastatic breast cancer, yet metastatic LN involvement cannot be discerned definitively using diagnostic imaging. This study investigated whether in vivo CEST may discriminate LNs with versus without metastatic involvement. METHODS: 3T MRI was performed in patients with breast cancer before clinically-indicated mastectomy or lumpectomy with LN removal, after which LN metastasic involvement was determined using histological evaluation. Non-contrast anatomical imaging, as well as B0 and B1 field maps, were acquired in sequence with three-point CEST-Dixon (3D turbo-gradient-echo; factor = 25; TR/TE1/ΔTE = 851/1.35/1.1 ms; spatial-resolution = 2.5 × 2.5 × 6 mm; slices = 10; four sinc-gauss pulses with duty-cycle = 0.5, total saturation duration = 701.7 ms; B1 = 1.5 µT; saturation offsets = -5.5 to +5.5 ppm; stepsize = 0.2 ppm; scan duration = 6 min 30 s). The mean z-spectrum from LNs with (n = 20) versus without (n = 22) metastatic involvement were analyzed and a Wilcoxon rank-sum test (significance: p < 0.05) was applied to evaluate differences in B0, B1 , and magnetization transfer ratio (MTR) in differing spectral regions of known proton exchange (nuclear Overhauser effect [NOE], amide, amine, and hydroxyl) between cohorts. RESULTS: No difference in axillary B1 (p = 0.634) or B0 (p = 0.689) was observed between cohorts. Elevated MTR was observed for the NOE (-1.7 ppm; MTR = 0.285 ± 0.075 vs. 0.248 ± 0.039; p = 0.048), amine (+2.5 ppm; MTR = 0.284 ± 0.067 vs. 0.234 ± 0.31; p = 0.005), and hydroxyl (+1 ppm; MTR = 0.394 ± 0.075 vs. 0.329 ± 0.055; p = 0.002) protons in LNs from participants with versus without metastatic involvement. CONCLUSIONS: Findings are consistent with a unique metastatic LN microenvironment detectable by CEST-Dixon and suggest that CEST MRI may have potential for mapping LN metastasis non-invasively in vivo.

Silent infarction in sickle cell disease is associated with brain volume loss in excess of infarct volume.

Introduction: Sickle cell disease (SCD) increases cerebral infarct risk, but reported effects on brain volume have varied. More detailed information using larger cohorts and contemporary methods could motivate the use of longitudinal brain volume assessment in SCD as an automated marker of disease stability or future progression. The purpose of this study was to rigorously evaluate whether children and young adults with SCD have reduced gray matter volume (GMV) and white matter volume (WMV) compared to healthy controls using high-resolution MRI. We tested the hypotheses that (i) elevated CBF, a marker of cerebral hemodynamic compensation in SCD, is associated with global and regional brain atrophy, and (ii) silent cerebral infarct burden is associated with brain atrophy in excess of infarct volume. Methods: Healthy controls (n = 49) and SCD participants without overt stroke (n = 88) aged 7-32 years completed 3 T brain MRI; pseudocontinuous arterial spin labeling measured CBF. Multivariable linear regressions assessed associations of independent variables with GMV, WMV, and volumes of cortical/subcortical regions. Results: Reduced hemoglobin was associated with reductions in both GMV (p = 0.032) and WMV (p = 0.005); reduced arterial oxygen content (CaO2) was also associated with reductions in GMV (p = 0.035) and WMV (p = 0.006). Elevated gray matter CBF was associated with reduced WMV (p = 0.018). Infarct burden was associated with reductions in WMV 30-fold greater than the infarct volume itself (p = 0.005). Increased GM CBF correlated with volumetric reductions of the insula and left and right caudate nuclei (p = 0.017, 0.017, 0.036, respectively). Infarct burden was associated with reduced left and right nucleus accumbens, right thalamus, and anterior corpus callosum volumes (p = 0.002, 0.002, 0.009, 0.002, respectively). Discussion: We demonstrate that anemia and decreased CaO2 are associated with reductions in GMV and WMV in SCD. Increased CBF and infarct burden were also associated with reduced volume in subcortical structures. Global WMV deficits associated with infarct burden far exceed infarct volume itself. Hemodynamic compensation via increased cerebral blood flow in SCD seems inadequate to prevent brain volume loss. Our work highlights that silent cerebral infarcts are just a portion of the brain injury that occurs in SCD; brain volume is another potential biomarker of brain injury in SCD.

Elevated magnetic resonance imaging measures of adipose tissue deposition in women with breast cancer treatment-related lymphedema.

PURPOSE: Breast cancer treatment-related lymphedema (BCRL) is a common co-morbidity of breast cancer therapies, yet factors that contribute to BCRL progression remain incompletely characterized. We investigated whether magnetic resonance imaging (MRI) measures of subcutaneous adipose tissue were uniquely elevated in women with BCRL. METHODS: MRI at 3.0 T of upper extremity and torso anatomy, fat and muscle tissue composition, and T2 relaxometry were applied in left and right axillae of healthy control (n = 24) and symptomatic BCRL (n = 22) participants to test the primary hypothesis that fat-to-muscle volume fraction is elevated in symptomatic BCRL relative to healthy participants, and the secondary hypothesis that fat-to-muscle volume fraction is correlated with MR relaxometry of affected tissues and BCRL stage (significance criterion: two-sided p < 0.05). RESULTS: Fat-to-muscle volume fraction in healthy participants was symmetric in the right and left sides (p = 0.51); in BCRL participants matched for age, sex, and BMI, fat-to-muscle volume fraction was elevated on the affected side (fraction = 0.732 ± 0.184) versus right and left side in controls (fraction = 0.545 ± 0.221, p < 0.001). Fat-to-muscle volume fraction directly correlated with muscle T2 (p = 0.046) and increased with increasing level of BCRL stage (p = 0.041). CONCLUSION: Adiposity quantified by MRI is elevated in the affected upper extremity of women with BCRL and may provide a surrogate marker of condition onset or severity. CLINICAL TRIAL: NCT02611557.