Cerebral hemodynamic changes after haploidentical hematopoietic stem cell transplant in adults with sickle cell disease.

ABSTRACT: Preliminary evidence from a series of 4 adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics. HSCT largely normalizes cerebral hemodynamics in children with SCD. We tested the hypothesis in adults with SCD that cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) measured using magnetic resonance imaging, normalized to healthy values, comparing measurements from ∼1 month before to 12 to 24 months after HSCT (n = 11; age, 33.3 ± 8.9 years; 389 ± 150 days after HSCT) with age-, race- and sex-matched values from healthy adults without sickle trait (n = 28; age, 30.2 ± 5.6 years). Before transplant, 7 patients had neurological indications for transplant (eg, overt stroke) and 4 had nonneurological reasons for haploidentical bone marrow transplant (haplo-BMT). All received haplo-BMT from first-degree relatives (parent, sibling, or child donor) with reduced-intensity preparation and maintained engraftment. Before transplant, CBF was elevated (CBF, 69.11 ± 24.7 mL/100 g/min) compared with that of controls (P = .004). Mean CBF declined significantly after haplo-BMT (posttransplant CBF, 48.2 ± 13.9 mL/100 g/min; P = .003). OEF was not different from that of controls at baseline and did not change significantly after haplo-BMT (pretransplant, 43.1 ± 6.7%; posttransplant, 39.6 ± 7.0%; P = .34). After transplant, CBF and OEF were not significantly different from controls (CBF, 48.2 ± 13.4 mL/100 g/min; P = .78; and OEF, 39.6 ± 7.0%; P > .99). CMRO2 did not change significantly after haplo-BMT (pretransplant, 3.18 ± 0.87 mL O2/100 g/min; posttransplant, 2.95 ± 0.83; P = .56). Major complications of haplo-BMT included 1 infection-related death and 1 severe chronic graft-versus-host disease. Haplo-BMT in adults with SCD reduces CBF to that of control values and maintains OEF and CMRO2 on average at levels observed in healthy adult controls. The trial was registered at www.clinicaltrials.gov as #NCT01850108.

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.

Subcutaneous Adipose Tissue Edema in Lipedema Revealed by Noninvasive 3T MR Lymphangiography.

BACKGROUND: Lipedema exhibits excessive lower-extremity subcutaneous adipose tissue (SAT) deposition, which is frequently misidentified as obesity until lymphedema presents. MR lymphangiography may have relevance to distinguish lipedema from obesity or lymphedema. HYPOTHESIS: Hyperintensity profiles on 3T MR lymphangiography can identify distinct features consistent with SAT edema in participants with lipedema. STUDY TYPE: Prospective cross-sectional study. SUBJECTS: Participants (48 females, matched for age [mean = 44.8 years]) with lipedema (n = 14), lipedema with lymphedema (LWL, n = 12), cancer treatment-related lymphedema (lymphedema, n = 8), and controls without these conditions (n = 14). FIELD STRENGTH/SEQUENCE: 3T MR lymphangiography (nontracer 3D turbo-spin-echo). ASSESSMENT: Review of lymphangiograms in lower extremities by three radiologists was performed independently. Spatial patterns of hyperintense signal within the SAT were scored for extravascular (focal, diffuse, or not apparent) and vascular (linear, dilated, or not apparent) image features. STATISTICAL TESTS: Interreader reliability was computed using Fleiss Kappa. Fisher's exact test was used to evaluate the proportion of image features between study groups. Multinomial logistic regression was used to assess the relationship between image features and study groups. The odds ratio (OR) and 95% confidence interval (CI) of SAT extravascular and vascular features was reported in groups compared to lipedema. The threshold of statistical significance was P < 0.05. RESULTS: Reliable agreement was demonstrated between three independent, blinded reviewers (P < 0.001). The frequency of SAT hyperintensities in participants with lipedema (36% focal, 36% diffuse), LWL (42% focal, 33% diffuse), lymphedema (62% focal, 38% diffuse), and controls (43% focal, 0% diffuse) was significantly distinct. Compared with lipedema, SAT hyperintensities were less frequent in controls (focal: OR = 0.63, CI = 0.11-3.41; diffuse: OR = 0.05, CI = 0.00-1.27), similar in LWL (focal: OR = 1.29, CI = 0.19-8.89; diffuse: OR = 1.05, CI = 0.15-7.61), and more frequent in lymphedema (focal: OR = 9.00, CI = 0.30-274.12; diffuse: OR = 5.73, CI = 0.18-186.84). DATA CONCLUSION: Noninvasive MR lymphangiography identifies distinct signal patterns indicating SAT edema and lymphatic load in participants with lipedema. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

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.

Magnetic resonance imaging and bioimpedance evaluation of lymphatic abnormalities in patients with breast cancer treatment-related lymphedema.

PURPOSE: Breast cancer treatment-related lymphedema (BCRL) evaluation is frequently performed using portable measures of limb volume and bioimpedance asymmetry. Here quantitative magnetic resonance imaging (MRI) is applied to evaluate deep and superficial tissue impairment, in both surgical and contralateral quadrants, to test the hypothesis that BCRL impairment is frequently bilateral and extends beyond regions commonly evaluated with portable external devices. METHODS: 3-T MRI was applied to investigate BCRL topographical impairment. Female BCRL (n = 33; age = 54.1 ± 11.2 years; stage = 1.5 ± 0.8) and healthy (n = 33; age = 49.4 ± 11.0 years) participants underwent quantitative upper limb MRI relaxometry (T2), bioimpedance asymmetry, arm volume asymmetry, and physical evaluation. Parametric tests were applied to evaluate study measurements (i) between BCRL and healthy participants, (ii) between surgical and contralateral limbs, and (iii) in relation to clinical indicators of disease severity. Two-sided p-value < 0.05 was required for significance. RESULTS: Bioimpedance asymmetry was significantly correlated with MRI-measured water relaxation (T2) in superficial tissue. Deep muscle (T2 = 37.6 ± 3.5 ms) and superficial tissue (T2 = 49.8 ± 13.2 ms) relaxation times were symmetric in healthy participants. In the surgical limbs of BCRL participants, deep muscle (T2 = 40.5 ± 4.9 ms) and superficial tissue (T2 = 56.0 ± 14.8 ms) relaxation times were elevated compared to healthy participants, consistent with an edematous micro-environment. This elevation was also observed in contralateral limbs of BCRL participants (deep muscle T2 = 40.3 ± 5.7 ms; superficial T2 = 56.6 ± 13.8 ms). CONCLUSIONS: Regional MRI measures substantiate a growing literature speculating that superficial and deep tissue, in surgical and contralateral quadrants, is affected in BCRL. The implications of these findings in the context of titrating treatment regimens and understanding malignancy recurrence are discussed.

Factors Related to Injury Prevention Programming by Missouri School Nurses.

Schools often offer injury prevention (IP) programs, but little is known about the types of programs provided or how school nurses decide which to choose. Nurses in the Missouri School Health Services Staffing Survey Database were sent a survey in spring, 2011, to describe school-based IP efforts being offered. A multivariate linear regression was conducted to delineate factors associated with offering IP programs. In total, 522 school nurses participated (33% response rate). The highest priority for selecting an IP program was perceived program effectiveness (92.3% agreement, n = 482). Determinants of offering IP programs included being asked to identify a speaker, being a high school, receiving funding in the last year, prioritizing evidence-based programs, perceiving that administrators support professional development, and knowing how to address patterns of injuries. School nurses should be competent in planning, implementing, and evaluating IP programs, and additional training may be required to accomplish this.