T2-fluid attenuated inversion recovery mismatch in tumefactive multiple sclerosis.

The T2-fluid attenuated inversion recovery (FLAIR) mismatch sign has been suggested as an imaging marker of isocitrate dehydrogenase-mutant 1p/19q non-codeleted gliomas with 100% specificity. Tumefactive demyelination is a common mimic of neoplasm that has led to unnecessary biopsies and even resections. We report a case of tumefactive multiple sclerosis in a 46-year-old male without prior symptomatic demyelinating episodes that demonstrates the T2-FLAIR mismatch sign. Our findings suggest the T2-FLAIR mismatch sign should not be used as a differential feature between glioma and tumefactive demyelination. Because typical isocitrate dehydrogenase-mutant 1p/19q non-codeleted gliomas typically do not demonstrate significant enhancement, such diagnosis should be reserved when post-contrast images are unavailable.

Imaging Considerations in Spinal Cord Evaluation.

Multiple diverse pathologies result in the clinical presentation of myelopathy. The preferred way to image the spinal cord depends on clinical history, anatomic site of interest, and patient issues limiting certain imaging modalities. This radiology-focused article discusses pertinent physiological considerations, reviews basic and newer imaging techniques, and examines several distinct disease entities in order to highlight the key role of imaging in the work-up of myelopathy.

Clinical and Imaging Features of Non-Small-Cell Lung Cancer in Young Patients.

BACKGROUND: Non-small-cell lung cancer (NSCLC) in young adult patients is rare, with scarce data available in patients aged < 40 years and even less in those aged < 35 years. Our goal was to determine the presenting symptoms, clinicopathologic characteristics, and imaging features of young patients with NSCLC at time of diagnosis and compare them to those of older adults. PATIENTS AND METHODS: We retrospectively analyzed the medical records and imaging of young patients (≤ 40 years old) with NSCLC treated at our institution between 1998 and 2018. Patients < 35 years old were compared to those between 35 and 40 years old. Characteristics of patients ≤ 40 years old were compared to older patients (> 40 years) from publicly available data sets. RESULTS: We identified 166 young patients with NSCLC (median age, 36.6 years; range, 18-40 years). Most presented with nonspecific respiratory symptoms and were diagnosed with pneumonia (84/136, 62%). Compared to patients < 35 years old, patients 35-40 years old were more likely to have malignancy detected incidentally (15% vs. 5%, P = .04). Patients < 35 years old were more likely to have central tumors (55% vs. 33%, P = .02) and to have bone (38% vs. 19%, P = .007) and lung (39% vs. 24%, P = .03) metastases. Compared to older patients (> 40 years), young patients were more likely to be never smokers (65.0% vs. 14.7%, P < .001) and to have advanced disease (88% vs. 66%, P < .001). CONCLUSION: Young patients with NSCLC often present with nonspecific symptoms and have advanced disease at diagnosis, often mimicking other pathologies. Awareness of the clinical presentation and imaging features of NSCLC in young patients may help minimize delays in diagnoses.

Perinatal maternal undernutrition does not result in offspring capillary rarefaction in the middle-aged male baboon at rest.

Microvascular health is a main determinant of coronary blood flow reserve and myocardial vascular resistance. Extracardiac capillary abnormality has been reported in subjects at increased coronary heart disease risk, such as prehypertension, hypertension, diabetes, hyperlipidemia, and atherosclerosis. We have reported cardiovascular dysfunction in a cohort of maternal nutrient reduction (MNR)-induced intrauterine growth restriction (IUGR) baboon offspring. Here we test the hypothesis that there is oral capillary rarefaction associated with MNR-induced IUGR. Capillary density was quantified using in vivo high-power capillaroscopy on seven middle-aged (~10.7 yr; human equivalent ~40 yr) male IUGR baboons and seven male age-matched controls in the lateral buccal and inferior labial mucosa. While no difference was found between groups in either area by fraction area or optical density for these vascular beds derived from fetal preductal vessels, further studies are needed on post-ductal vascular beds, retina, and function.

The nonhuman primate hypothalamo-pituitary-adrenal axis is an orchestrator of programming-aging interactions: role of nutrition.

Developmental programming alters life-course multi-organ function and significantly affects life-course health. Recently, interest has developed in how programming may influence the rate of aging. This review describes interactions of nutrition and programming-aging interactions in hypothalamo-pituitary-adrenal (HPA) development and function from fetal development to old age. A full picture of these interactions requires data on levels of HPA activity relating to the hypothalamic, adrenal cortical, circulating blood, and peripheral cortisol metabolism. Data are provided from studies on our baboon, nonhuman primate model both across the normal life course and in offspring of maternal baboons who were moderately undernourished by a global 30% diet reduction during pregnancy and lactation. Sex differences in offspring outcomes in response to similar challenges are described. The data clearly show programming of increased HPA axis activity by moderate maternal undernutrition. Increased postnatal circulating cortisol concentrations are related to accelerated aging of the brain and cardiovascular systems. Future studies should address peripheral cortisol production and the influence of aging advantage in females. These data support the view that the HPA is an orchestrator of interactions of programming-aging mechanisms.

Target-specific yield rate and clinical utility of percutaneous tissue sampling in spinal infection.

BACKGROUND: Percutaneous tissue sampling in spondylodiscitis is frequently performed but with highly variable yield in literature and unclear clinical impact. Factors that influence the culture success rate are not well established. OBJECTIVE: To determine target specific yield and clinical impact of percutaneous biopsy in clinically and imaging diagnosed spinal infection and factors that may influence the yield rate. METHODS: Institutional review board approved single center retrospective chart review from 2015 to 2019 analyzing imaging findings, clinical notes, procedural reports, and laboratory results on cases of concurrent imaging and clinically diagnosed spondylodiscitis that underwent percutaneous tissue sampling. RESULTS: A total of 111 patients and 189 specimens were analyzed. The overall culture yield in spondylodiscitis was approximately 27%, 9% affecting management. Abscess/fluid and septic arthritis aspirations had higher yield rates compared to soft tissue/phlegmon aspirations. Core sampling of the bone and disc yielded positive culture 12% of the time, 2% resulted in change in management. Upper thoracic spine biopsies were more frequently positive and associated with change in management. Positive culture elsewhere in the body represented the major reason underlying lack of clinical impact. Lack of prior antibiotic treatment and diabetes mellitus demonstrated a trend toward higher culture positivity, although a larger sample size is needed to confirm these findings. No repeat biopsy yielded positive culture. Staphylococcus spp. accounted for approximately half of the microorganisms cultured. In positive biopsies where infection was also found elsewhere in the body, the organism was nearly always congruent (96%).

Not hepatic infarction: Cold quadrate sign.

A 50-year-old male presented with bilateral lower extremity plain is found to have a wedge-shape hypodense region in the hepatic quadrate lobe. The hypoenhancement was thought to be a result of systemic-portal venous shunting due to IVC obstruction, a "cold" version of the classically described hot quadrate sign. Follow-up CT confirmed the diagnosis. Venous drainage pathway for both hot and cold quadrate signs is discussed.

Vascular magnetic resonance angiography techniques.

Magnetic resonance angiography (MRA) denotes a unique option for the evaluation of peripheral vasculature due to its noninvasive nature, lack of ionizing radiation exposure, potential for non-contrast examination, and ability for generating volumetric representations that showcase vascular pathology. The constant evolution of the available MRA techniques, however, makes understanding and determining an optimal imaging protocol difficult. Here we present a brief overview of the major MRA sequence options, their major weaknesses and strengths, and related imaging considerations. Understanding the technical underpinnings of the various MRA methods helps with recognition of common imaging issues and artifacts and rendering clinically relevant interpretations.

Systematic review of civilian intravascular ballistic embolism reports during the last 30 years.

BACKGROUND: Intravascular ballistic embolization is a rare complication of missile injury. Because of its rarity, much remains to be known about its presentation, pathophysiology, complications, and management. In this study, we analyze case reports of ballistic embolization in the last 30 years and available cases from our institution to determine the likely patient, the nature of the embolization, the possible complications, and a general management strategy. METHODS: A PubMed search was performed in search of missile embolization cases from 1988 to 2018 in the English language, including only cases of intravascular emboli. Cases resulting from combat and explosive devices were excluded. In addition, five cases from our institution were included in the analysis. RESULTS: A total of 261 cases were analyzed. The most common presentation was that of a young man (reflecting the demographics of those sustaining gunshot wound injuries) with injury to the anterior torso from a single gunshot wound. Venous entry was most common, most often through large-caliber vessels. There was roughly equal involvement of the right and left circulation. Left circulation emboli were frequently symptomatic, with ischemia being the most frequent sequela. In contrast, a right circulation embolus was rarely associated with significant complications. CONCLUSIONS: Despite its rarity, ballistic embolization should be considered in gunshot injury with known large-vessel injury when an exit wound is not identified. In particular, signs of ischemia distant from the injury site warrant timely investigation to maximize tissue salvageability. We present a management strategy model for consideration.

Antenatal Synthetic Glucocorticoid Exposure at Human Therapeutic Equivalent Doses Predisposes Middle-Age Male Offspring Baboons to an Obese Phenotype That Emerges With Aging.

INTRODUCTION: Women threatening premature delivery receive synthetic glucocorticoids (sGC) to accelerate fetal lung maturation, reducing neonatal mortality and morbidity. Few investigations have explored potential long-term offspring side effects. We previously reported increased pericardial fat and liver lipids in 10-year-old (human equivalent 40 years) male baboons exposed to 3 antenatal sGC courses. We hypothesized middle-aged sGC male offspring show obesity-related morphometric changes. METHODS: Pregnant baboons received courses of 2 betamethasone injections (175 µg·kg-1·d-1 intramuscular) at 0.6, 0.64, and 0.68 gestation. At 10 to 12.5 years, we measured morphometrics and serum lipids in 5 sGC-exposed males and 10 age-matched controls. We determined whether morphometric parameters predicted amount of pericardial fat or lipids. Life-course serum lipids were measured in 25 males (7-23 years) providing normal regression formulas to compare sGC baboons' lipid biological and chronological age. RESULTS: Birth weights were similar. When studied, sGC-exposed males showed a steeper weight increase from 8 to 12 years and had increased waist and hip circumferences, neck and triceps skinfolds, and total and low-density lipoprotein cholesterol. Triceps skinfold correlated with apical and midventricular pericardial fat thickness, hip and waist circumferences with insulin. CONCLUSIONS: Triceps skinfold and waist and hip circumferences are useful biomarkers for identifying individuals at risk for obesity and metabolic dysregulation following fetal sGC exposure. Prenatal sGC exposure predisposes male offspring to internal adiposity, greater body size, and increased serum lipids. Results provide further evidence for developmental programming by fetal sGC exposure and call attention to potential emergence of adverse life-course effects.

Ageing changes in biventricular cardiac function in male and female baboons (Papio spp.).

KEY POINTS: Life course changes in cardiovascular function in a non-human primate have been comprehensively characterized. Age-related declines in normalized left ventricular stroke volume and cardiac output were found with corresponding decreases in biventricular ejection fractions and filling rates. There were age-related decreases in male and female baboon normalized left ventricular myocardial mass index, which declined at similar rates. Systolic functional declines in right ventricular function were observed with age, similar to the left ventricle. Sex differences were found in the rates and directions of right ventricular volume changes along with decreased end-systolic right ventricular sphericity. The results validate the baboon as an appropriate model for translational studies of cardiovascular functional decline with ageing. ABSTRACT: Previous studies reported cardiac function declines with ageing. This study determined changes in biventricular cardiac function in a well-characterized baboon model. Cardiac magnetic resonance imaging measured key biventricular parameters in 47 baboons (22 female, age 4-23 years). ANCOVA assessed sex and age changes with P < 0.05 deemed significant. Stroke volume, cardiac output and other cardiac functional parameters were normalized to body surface area. There were similar, age-related rates of decrease in male (M) and female (F) normalized left ventricular (LV) myocardial mass index (M: -1.2 g m-2  year-1 , F: -0.9 g m-2  year-1 ). LV ejection fraction declined at -0.96% year-1 (r = -0.43, P = 0.002) and right ventricular (RV) ejection fraction decreased at -1.2% year-1 (r = -0.58, P < 0.001). Normalized LV stroke volume fell at -1.1 ml m-2  year-1 (r = -0.47, P = 0.001), normalized LV ejection rate at -3.8 ml s-1  m-2  year-1 (r = -0.43, P < 0.005) and normalized LV filling rate at -4.1 ml s-1  m-2  year-1 (r = -0.44, P < 0.005). Also, RV wall thickening fraction decreased with age (slope = -1% year-1 , P = 0.008). RV ejection rate decreased at -3.6 ml s-1  m-2  year-1 (P = 0.002) and the normalized average RV filling rate dropped at -3.7 ml s-1  m-2  year-1 (P < 0.0001). End-systolic RV sphericity index also dropped with age (r = -0.33, P = 0.02). Many observed changes parallel previously reported data in human and animal studies. These measured biventricular functional declines in hearts with ageing from the closest experimental primate species to man underscore the utility of the baboon model for investigating mechanisms related to heart ageing.

Sex-dimorphic acceleration of pericardial, subcutaneous, and plasma lipid increase in offspring of poorly nourished baboons.

Developmental programming by reduced maternal nutrition alters function in multiple offspring physiological systems, including lipid metabolism. We have shown that intrauterine growth restriction (IUGR) leads to offspring cardiovascular dysfunction with an accelerated aging phenotype in our nonhuman primate, baboon model. We hypothesized age-advanced pericardial fat and blood lipid changes. In pregnancy and lactation, pregnant baboons ate ad lib (control) or 70% ad lib diet (IUGR). We studied baboon offspring pericardial lipid deposition with magnetic resonance imaging at 5-6 years (human equivalent 20-24 years), skinfold thickness, and serum lipid profile at 8-9 years (human equivalent 32-36 years), comparing values with a normative life-course baboon cohort, 4-23 years. Increased pericardial fat deposition occurred in IUGR males but not females. Female but not male total cholesterol, low-density lipoprotein, and subcutaneous fat were increased with a trend of triglycerides increase. When comparing IUGR changes to values in normal older baboons, the increase in male apical pericardial fat was equivalent to advancing age by 6 years and the increase in female low-density lipoprotein to an increase of 3 years. We conclude that reduced maternal diet accelerates offspring lipid changes in a sex-dimorphic manner. The interaction between programming and accelerated lipogenesis warrants further investigation.

Intrauterine growth restriction results in persistent vascular mismatch in adulthood.

KEY POINTS: Intrauterine growth restriction (IUGR) increases offspring risk of chronic diseases later in life, including cardiovascular dysfunction. Our prior studies suggest biventricular cardiac dysfunction and vascular impairment in baboons who were IUGR at birth because of moderate maternal nutrient reduction. The current study reveals changes in artery sizes, distensibility, and blood flow pattern in young adult IUGR baboons, which may contribute to cardiac stress. The pattern of abnormality observed suggests that vascular redistribution seen with IUGR in fetal life may continue into adulthood. ABSTRACT: Maternal nutrient reduction induces intrauterine growth restriction (IUGR), increasing risks of chronic diseases later in life, including cardiovascular dysfunction. Using ultrasound, we determined regional blood flow, blood vessel sizes, and distensibility in IUGR baboons (8 males, 8 females, 8.8 years, similar to 35 human years) and controls (12 males, 12 females, 9.5 years). The measured blood vessels were larger in size in the males compared to females before but not after normalization to body surface area. Smaller IUGR normalized blood vessel sizes were observed in the femoral and external iliac arteries but not the brachial or common carotid arteries and not correlated significantly with birth weight. Mild decrease in distensibility in the IUGR group was seen in the iliac but not the carotid arteries without between-sex differences. In IUGR baboons there was increased carotid arterial blood flow velocity during late systole and diastole. Overall, our findings support the conclusion that region specific vascular and haemodynamic changes occur with IUGR, which may contribute to the occurrence of later life cardiac dysfunction. The pattern of alteration observed suggests vascular redistribution efforts in response to challenges in the perinatal period may persist into adulthood. Further studies are needed to determine the life course progression of these changes.

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition.

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4-7 years; human equivalent 14-24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years (p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans.

Maternal nutrient restriction during pregnancy and lactation leads to impaired right ventricular function in young adult baboons.

KEY POINTS: Maternal nutrient restriction induces intrauterine growth restriction (IUGR) and leads to heightened cardiovascular risks later in life. We report right ventricular (RV) filling and ejection abnormalities in IUGR young adult baboons using cardiac magnetic resonance imaging. Both functional and morphological indicators of poor RV function were seen, many of which were similar to effects of ageing, but also with a few key differences. We observed more pronounced RV changes compared to our previous report of the left ventricle, suggesting there is likely to be a component of isolated RV abnormality in addition to expected haemodynamic sequelae from left ventricular dysfunction. In particular, our findings raise the suspicion of pulmonary hypertension after IUGR. This study establishes that IUGR also leads to impairment of the right ventricle in addition to the left ventricle classically studied. ABSTRACT: Maternal nutrient restriction induces intrauterine growth restriction (IUGR), increasing later life chronic disease including cardiovascular dysfunction. Our left ventricular (LV) CMRI studies in IUGR baboons (8 M, 8 F, 5.7 years - human equivalent approximately 25 years), control offspring (8 M, 8 F, 5.6 years), and normal elderly (OLD) baboons (6 M, 6 F, mean 15.9 years) revealed long-term LV abnormalities in IUGR offspring. Although it is known that right ventricular (RV) function is dependent on LV health, the IUGR right ventricle remains poorly studied. We examined the right ventricle with cardiac magnetic resonance imaging in the same cohorts. We observed decreased ejection fraction (49 ± 2 vs. 33 ± 3%, P < 0.001), cardiac index (2.73 ± 0.27 vs. 1.89 ± 0.20 l min-1 m-2 , P < 0.05), early filling rate/body surface area (BSA) (109.2 ± 7.8 vs. 44.6 ± 7.3 ml s-1  m-2 , P < 0.001), wall thickening (61 ± 3 vs. 44 ± 5%, P < 0.05), and longitudinal shortening (26 ± 3 vs. 15 ± 2%, P < 0.01) in IUGR animals with increased chamber volumes. Many, but not all, of these changes share similarities to normal older animals. Our findings suggest IUGR-induced pulmonary hypertension should be further investigated and that atrial volume, pulmonic outflow and interventricular septal motion may provide valuable insights into IUGR cardiovascular physiology. Overall, our findings reaffirm that gestational and neonatal challenges can result in long-term programming of poor offspring cardiovascular health. To our knowledge, this is the first study reporting IUGR-induced programmed adult RV dysfunction in an experimental primate model.

The Radiologic and Pathologic Diagnosis of Biphasic Pulmonary Blastoma.

Pulmonary blastomas are rare malignancies, representing 0.25% to 0.5% of all primary lung neoplasms with often aggressive progression and poor prognosis. Clinical management of pulmonary blastomas depends on histologic subtype, staging, and presentation, and may consist of surgery, chemotherapy, and radiation. Biphasic pulmonary blastoma is a subtype of pulmonary blastoma that exhibits biphasic histology, with both epithelial and mesenchymal malignant elements. We report a case of biphasic pulmonary blastoma in a 33-year-old female with 1 pack per day history of smoking for approximately 16 years, who presented with left-sided pleuritic chest pain on deep inspiration without otherwise significant pat medical history. Imaging evaluation using chest radiography, computed tomography, and magnetic resonance imaging identified a heterogenous, well-circumscribed, left lower lobe mass with extensive necrosis and hemorrhage. No lymphadenopathy or distant metastasis was detected through imaging evaluation. Surgical resection of the tumor followed by histopathological analysis confirmed a biphasic pulmonary blastoma.

Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing.

KEY POINTS: Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short-term and long-term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental-fetal development indicate a need for models in precocial species for translation to human development. We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood. Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls. Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort. Understanding early cardiac biomarkers of IUGR using non-invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies. ABSTRACT: Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group and sex (with P < 0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in control but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodelling, reduces systolic and diastolic function, and results in the emergence of a premature ageing phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with ageing in an IUGR non-human primate model. Further studies across the life span will determine progression of cardiac dysfunction.