Sexually Dimorphic Patterns of Cell Proliferation in the Brain Are Linked to Seasonal Life-History Transitions in Red-Sided Garter Snakes.

Seasonal rhythms in physiology and behavior are widespread across diverse taxonomic groups and may be mediated by seasonal changes in neurogenesis, including cell proliferation, migration, and differentiation. We examined if cell proliferation in the brain is associated with the seasonal life-history transition from spring breeding to migration and summer foraging in a free-ranging population of red-sided garter snakes (Thamnophis sirtalis) in Manitoba, Canada. We used the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to label newly proliferated cells within the brain of adult snakes collected from the den during the mating season or from a road located along their migratory route. To assess rates of cell migration, we further categorized BrdU-labeled cells according to their location within the ventricular zone or parenchymal region of the nucleus sphericus (homolog of the amygdala), preoptic area/hypothalamus, septal nucleus, and cortex (homolog of the hippocampus). We found that cell proliferation and cell migration varied significantly with sex, the migratory status of snakes, and reproductive behavior in males. In most regions of interest, patterns of cell proliferation were sexually dimorphic, with males having significantly more BrdU-labeled cells than females prior to migration. However, during the initial stages of migration, females exhibited a significant increase in cell proliferation within the nucleus sphericus, hypothalamus, and septal nucleus, but not in any subregion of the cortex. In contrast, migrating males exhibited a significant increase in cell proliferation within the medial cortex but no other brain region. Because it is unlikely that the medial cortex plays a sexually dimorphic role in spatial memory during spring migration, we speculate that cell proliferation within the male medial cortex is associated with regulation of the hypothalamus-pituitary-adrenal axis. Finally, the only brain region where cell migration into the parenchymal region varied significantly with sex or migratory status was the hypothalamus. These results suggest that the migration of newly proliferated cells and/or the continued division of undifferentiated cells are activated earlier or to a greater extent in the hypothalamus. Our data suggest that sexually dimorphic changes in cell proliferation and cell migration in the adult brain may mediate sex differences in the timing of seasonal life-history transitions.

Sonographic-MRI Correlation After Percutaneous Sampling of Targeted Breast Ultrasound Lesions: Initial Experiences With Limited-Sequence Unenhanced MRI for Postprocedural Clip Localization.

OBJECTIVE: The purpose of this study is to determine the frequency of correlation of sonographic and MRI findings after percutaneous sampling of presumed ultrasound correlates to suspicious lesions detected on breast MRI and to describe our initial experiences with limited-sequence MRI for postprocedural clip verification. MATERIALS AND METHODS: Between January 1, 2014, and March 31, 2016, a total of 1947 contrast-enhanced breast MRI examinations were performed, and 245 targeted ultrasound examinations were conducted to identify correlates to suspicious MRI findings. We retrospectively identified all lesions that underwent ultrasound-guided sampling of a presumed sonographic correlate and for which a subsequent postprocedural limited-sequence unenhanced MR image for clip localization was available. This consisted of a T1-weighted non-fat-saturated and a T2-weighted fat-saturated sequence. Frequencies of sonographic-MRI correlation were quantified. RESULTS: The study cohort consisted of 35 patients with 38 presumed correlates that underwent ultrasound-guided sampling with postprocedural MRI for clip verification. The mean time from percutaneous sampling to postprocedural MRI examination was 1 day. Ten presumed sonographic correlates (26%) were found to localize to a site distinct from the lesion originally identified on MRI. One of these discordant cases revealed malignancy on subsequent MRI-guided biopsy, whereas the presumed sonographic correlate was found to be benign. No patient or lesion characteristics were associated with significantly different frequencies of correlation. CONCLUSION: In our initial experiences with MRI performed for postprocedural clip verification, 26% of presumed correlates to suspicious lesions detected on MRI were not the actual correlate, and 10% of these discordant cases ultimately revealed malignancy. Radiologists should take caution presuming that lesions identified on ultrasound actually represent the suspicious lesions detected on MRI. MRI for clip verification may be useful if ultrasound-guided sampling is pursued.

Administration of growth factors promotes salisphere formation from irradiated parotid salivary glands.

Worldwide, 500,000 cases of head and neck cancer (HNC) are reported each year and the primary treatment for HNC is radiotherapy. Although the goal of radiotherapy is to target the tumor, secondary exposure occurs in surrounding normal tissues, such as the salivary glands. As a result, despite successful treatment of the cancer, patients are left with long-term side effects due to direct damage to the salivary glands. The effect is chronic and currently there is no treatment. Stem cells are an attractive therapeutic option for treatment of radiation-induced glandular dysfunction because of the potential to regenerate damaged cell populations and restore salivary gland function. However, limited knowledge about the endogenous stem cell population post irradiation hinders the development for stem cell-based therapies. In this study, an ex vivo sphere formation cell culture system was utilized to assess the self-renewal capacity of cells derived from parotid salivary glands at a chronic time point following radiation. Salivary glands from irradiated mice generate significantly fewer salispheres, but can be stimulated with fetal bovine serum (FBS) to generate an equivalent number of salispheres as unirradiated salivary glands. Interestingly, the number and size of salispheres formed is dependent on the concentration of FBS supplemented into the media. Salispheres derived from irradiated glands and cultured in FBS media were found to contain cells that proliferate and express progenitor and acinar cell markers such as Keratin 5, Keratin 14, Aquaporin 5, and NKCC1. Utilization of insulin-like growth factor (IGF1) injections following radiation treatment restores salivary gland function and improves salisphere generation. These findings indicate that stimulation of these cellular populations may provide a promising avenue for the development of cell-based therapies for radiation-induced salivary gland damage.

Diffusion-weighted MRI characteristics associated with prognostic pathological factors and recurrence risk in invasive ER+/HER2- breast cancers.

BACKGROUND: Hormone receptor-positive breast cancer is the most common subtype; better tools to identify which patients in this group would derive clear benefit from chemotherapy are needed. PURPOSE: To evaluate the prognostic potential of diffusion-weighted MRI (DWI) by investigating associations with pathologic biomarkers and a genomic assay for 10-year recurrence risk. STUDY TYPE: Retrospective. SUBJECTS: In all, 107 consecutive patients (from 2/2010 to 1/2013) with estrogen receptor (ER)-positive/HER2neu-negative invasive breast cancer who had the 21-gene recurrence score (RS) test (Oncotype DX, Genomic Health). FIELD STRENGTH/SEQUENCE: Each subject underwent presurgical 3T breast MRI, which included DWI (b = 0, 800 s/mm2 ). ASSESSMENT: Apparent diffusion coefficient (ADC) and contrast-to-noise ratio (CNR) were measured for each lesion by a fifth year radiology resident. Pathological markers (Nottingham histologic grade, Ki-67, RS) were determined from pathology reports. Medical records were reviewed to assess recurrence-free survival. STATISTICAL TESTS: RS was stratified into low (<18), moderate (18-30), and high (>30)-risk groups. Associations of DWI characteristics with pathologic biomarkers were evaluated by binary or ordinal logistic regression, as appropriate, with adjustment for multiple comparisons. Post-hoc comparisons between specific groups were also performed. RESULTS: ADCmean (odds ratio [OR] = 0.61 per 1 standard deviation [SD] increase, adj. P = 0.044) and CNR (OR = 1.76 per 1-SD increase, adj. P = 0.026) were significantly associated with increasing tumor grade. DWI CNR was also significantly associated with a high (Ki-67 ≥14%) proliferation rate (OR = 2.55 per 1-SD increase, adj. P = 0.026). While there were no statistically significant linear associations in ADC (adj. P = 0.80-0.85) and CNR (adj. P = 0.56) across all three RS groups by ordinal logistic regression, post-hoc analyses suggested that high RS lesions exhibited lower ADCmean (P = 0.037) and ADCmax (P = 0.004) values and higher CNR (P = 0.008) compared to lesions with a low or moderate RS. DATA CONCLUSION: DWI characteristics correlated with tumor grade, proliferation index, and RS, and may potentially help to identify those with highest recurrence risk and most potential benefit from chemotherapy. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage 3 J. Magn. Reson. Imaging 2017.

Diffusion-weighted imaging: Effects of intravascular contrast agents on apparent diffusion coefficient measures of breast malignancies at 3 Tesla.

BACKGROUND: To determine whether apparent diffusion coefficient (ADC) measures of breast lesions at 3 Tesla (T) are affected by gadolinium administration. METHODS: The study included 19 patients who underwent 3T MRI. Diffusion-weighted imaging (DWI) was acquired with b = 0, 100, and 800 s/mm(2) before and after a dynamic contrast-enhanced (DCE) sequence. ADC values were measured for each lesion and normal fibroglandular tissue. Pre- and postcontrast ADC measures were compared by Wilcoxon signed-rank test, and differences between groups were compared by Mann-Whitney U test; P < 0.05 was considered statistically significant. RESULTS: There was no significant difference in pre- and postcontrast ADC measured at b = 0, 100, 800 s/mm(2) for malignancies (median change: -0.4%, -0.01 × 10(-3) mm(2) /s, P = 0.40), but there was a slight increase in postcontrast ADC in normal tissue (+1.6%, +0.04 × 10(-3) mm(2) /s, P = 0.0006). Findings were similar for both lesions (-0.4%, -0.01 × 10(-3) mm(2) /s, P = 0.54) and normal tissue (+1.5%, +0.03 × 10(-3) mm(2) /s, P = 0.002) with ADC measured at b = 0,800 and also at b = 100, 800 s/mm(2) (lesions: +0.9%, +0.01 × 10(-3) mm(2) /s, P = 0.71; normal tissue: +1.8%, +0.03 × 10(-3) mm(2) /s, P = 0.005). For lesions, results were not affected by lesion size, type (mass versus nonmass enhancement), mean initial enhancement, late enhancement, or delayed enhancement rate on DCE-MRI (P > 0.05 for all). Normal tissue showed some trends with greater progressive enhancement rates and higher late enhancement levels correlating with greater increase in postcontrast ADC (P = 0.09 for both). CONCLUSION: Our results show that breast lesion ADC measures using our approach were not significantly altered following DCE-MRI at 3T, suggesting DWI and DCE-MRI can be performed in any order without affecting diagnostic criteria. However, influences of contrast on ADC measures in normal breast tissue were observed and require further investigation.

Pulmonary effects of i.v. injection of crushed oral tablets: "excipient lung disease".

OBJECTIVE: When crushed oral tablets are injected i.v., their filler material (excipient) can induce a potentially fatal foreign-body reaction in pulmonary arterioles, presenting as dyspnea and pulmonary hypertension with centrilobular nodules on CT. We will describe the imaging and pathologic features of "excipient lung disease." CONCLUSION: The radiologist has a critical role in recognizing and reporting excipient lung disease because the referring clinician may be unaware of the patient's i.v. drug abuse.

Craniocervical hyperpneumatization with concurrent pneumorrhachis, pneumomediastinum, and subcutaneous emphysema in a weightlifter.

BACKGROUND CONTEXT: Acquired hyperpneumatization of the skull base and upper cervical vertebrae is extremely rare and is thought to occur in patients who habitually perform the Valsalva maneuver or engage in repetitive positive pressure activities such as scuba diving or free diving. Craniocervical hyperpneumatization has been reported to cause intracranial and extracranial pneumatoceles but is not generally considered as a cause of pneumorrhachis (air in the spinal canal). Pneumorrhachis is relatively rare, and usually occurs in a localized form, either in the cervical spine secondary to skull base fractures or in the thoracic spine secondary to pneumomediastinum or pneumothorax. Here, we report a case of extensive pneumorrhachis extending from the skull base to the thoracolumbar junction in association with marked axio-atlanto-occipital hyperpneumatization and pneumomediastinum. This unique constellation of findings likely resulted from complications of the Valsalva maneuver during strenuous exercise. PURPOSE: To present a unique case of axio-atlanto-occipital hyperpneumatization with concurrent marked cervicothoracic pneumorrhachis, subcutaneous emphysema, and pneumomediastinum and to provide a review of the relevant literature, pathophysiology, and treatment strategies related to hyperpneumatization and pneumorrhachis. STUDY DESIGN/SETTING: A unique case report from an urban medical center. PATIENT SAMPLE: A single case. OUTCOME MEASURES: Imaging findings and clinical history. METHODS: Imaging data from a picture archiving and communication system and clinical data from an electronic medical record system were analyzed. RESULTS: A 58-year-old previously healthy man presented with 3 to 4 weeks of neck pain, shoulder pain, and intermittent hand and finger numbness that developed after weightlifting. On physical examination, he had mild hyperreflexia and decreased pinprick sensation within the T5-T8 dermatomes. Initial radiographic and computed tomography (CT) studies demonstrated extensive craniocervical hyperpneumatization involving the occipital bone, clivus, and C1 and C2 vertebral bodies. There was also pneumorrhachis extending throughout the entire cervical and thoracic spine, which caused moderate dural compression. Pneumomediastinum and subcutaneous emphysema were present. Maxillofacial CT showed dehiscent bone involving the dens, atlas, and occipital bone, with adjacent soft-tissue gas and pneumorrhachis. He was managed conservatively and advised to stop performing the Valsalva maneuver during weightlifting. His symptoms resolved, and follow-up imaging showed complete resolution of pneumorrhachis and partial reversal of hyperpneumatization. CONCLUSIONS: Craniocervical hyperpneumatization is a rare complication of the Valsalva maneuver. Most reported cases have involved only the skull base, or the skull base and C1, and many have been further complicated by microfractures leading to pneumocephalus or extracranial pneumatoceles. We present a unique case of extensive craniocervical hyperpneumatization that extended to the level of C2 and was complicated by microfractures causing severe pneumorrhachis. Concurrent pneumomediastinum in this case may have been an independent complication of the Valsalva maneuver, which could have contributed to pneumorrhachis. Alternatively, pneumomediastinum may have been caused by migration of gas through the neural foramen from the epidural space, driven by positive pressure generated by the one-way valve effect of the Eustachian tube during periods of exertion.