Age-Related Changes of Normal Cerebral and Cardiac Blood Flow in Children and Adults Aged 7 Months to 61 Years.

BACKGROUND: Cerebral and cardiac blood flow are important to the pathophysiology and development of cerebro- and cardiovascular diseases. The purpose of this study was to investigate the age dependence of normal cerebral and cardiac hemodynamics in children and adults over a broad range of ages. METHODS AND RESULTS: Overall, 52 children (aged 0.6-17.2 years) and 30 adults (aged 19.2-60.7 years) without cerebro- and cardiovascular diseases were included in this study. Intracranial 4-dimensional flow and cardiac 2-dimensional phase-contrast magnetic resonance imaging were performed for all participants to measure flow parameters in the major intracranial vessels and aorta. Total cerebral blood flow (TCBF), cardiac and cerebral indexes, brain volume, and global cerebral perfusion (TCBF/brain volume) were evaluated. Flow analysis revealed that TCBF increased significantly from age 7 months to 6 years (P<0.001) and declined thereafter (P<0.001). Both cardiac and cerebral indices declined with age (P<0.001). The ratio of TCBF to ascending aortic flow declined rapidly until age 18 years (P<0.001) and remained relatively stable thereafter. Age-related changes of cerebral vascular peak velocities exhibited a trend similar to TCBF. By comparison, aortic peak velocities maintained relatively high levels in children and declined with age in adults (P<0.001). TCBF significantly correlated with brain volume in adults (P=0.005) and in 2 pediatric subgroups, aged <7 years (P<0.001) and 7 to 18 years (P=0.039). CONCLUSIONS: Cerebral and cardiac flow parameters are highly associated with age. The findings collectively highlight the importance of age-matched control data for the characterization of intracranial and cardiac hemodynamics.

Complex Alterations of Intracranial 4-Dimensional Hemodynamics in Vein of Galen Aneurysmal Malformations During Staged Endovascular Embolization.

BACKGROUND: Vein of Galen aneurysmal malformations (VGAMs) are rare congenital cerebral arteriovenous shunts often treated by staged endovascular embolization early in life. Treatment-induced changes in intracranial hemodynamics and their impact on the clinical management of VGAM patients remain unclear. OBJECTIVE: To evaluate hemodynamic alterations in the cerebral arterial and venous network in pediatric patients with VGAMs during staged embolizations. METHODS: Serial 4-dimensional flow magnetic resonance imaging (21 scans) was performed in 6 VGAM patients (3 female; mean age, 2.1 ± 4.0 years) undergoing staged embolization. Time-integrated pathlines were used to visualize 3-dimensional blood flow changes in intracranial arterial and venous systems. Total cerebral arterial inflow (flow in bilateral internal carotid arteries plus basilar artery), arteriovenous shunt flow, and blood flow in other major cerebral arteries (middle cerebral artery; posterior cerebral artery) were quantified for all patients. RESULTS: Intracranial 3-dimensional blood flow visualization demonstrated marked reduction of arteriovenous shunting and distinct hemodynamic alterations after embolization. From baseline to endpoint embolization, total cerebral arterial inflow dropped by 40.2% (from 22.70 ± 6.54 mL/s to 13.57 ± 4.87 mL/s), corresponding to arteriovenous shunt flow reduction of 73.5% (from 9.69 ± 6.16 mL/s to 2.57 ± 3.79 mL/s). In addition, the ipsilateral posterior cerebral artery/middle cerebral artery flow ratio decreased by 86.9% (from 4.20 ± 6.28 to 0.55 ± 0.23). CONCLUSION: Hemodynamic alterations in VGAMs after embolization can be visualized and quantified using 4-dimensional flow magnetic resonance imaging. Cerebral arterial inflow and arteriovenous shunt flow reduction and complex flow redistribution after embolization illustrate the potential of 4-dimensional flow magnetic resonance imaging to better evaluate the efficacy of interventions and monitor treatment effects.

Safety of Blood Pool Contrast Agent Administration in Children and Young Adults.

OBJECTIVE: The objective of our study was to determine the adverse reaction rate associated with the administration of blood pool contrast material in children and young adults. MATERIALS AND METHODS: A review of the MRI and pharmacy databases identified all patients who received gadofosveset trisodium from October 1, 2011, to June 30, 2014. Patients were classified as having been anesthetized or not anesthetized for the MRI examinations. A review of the electronic medical records identified adverse reactions recorded within 24 hours of contrast administration. The adverse reactions were graded as mild, moderate, or severe. Risk ratios were calculated between the adverse reaction rate experienced by anesthetized patients and that experience by nonanesthetized patients. RESULTS: During the study period, 626 patients (mean age, 11.7 years) received 711 doses of gadofosveset trisodium; 137 adverse reactions were recorded, which yields a 19.3% (137/711) adverse reaction rate. There were 115 adverse reactions experienced by 367 anesthetized patients (31.3%): 93.0% (107/115) were mild and 7.0% (8/115) were moderate. The remaining 22 adverse reactions were experienced by 344 (6.4%) nonanesthetized patients, and 90.9% (20/22) were mild. Three nonanesthetized patients had allergiclike reactions; of these allergiclike reactions, one was mild and two were severe for a severe allergiclike reaction rate of 0.28% (2/711). Severe allergiclike reactions were treated without any adverse outcomes. Anesthetized patients were 5.7 times more likely to experience an adverse event than nonanesthetized patients; most reactions in anesthetized patients were seen after the administration of anesthesia alone. CONCLUSION: Most reactions after gadofosveset trisodium administration in children and young adults are mild; however, severe allergiclike reactions occur, so policies must be in place to treat patients with adverse reactions when using this contrast agent. These data may be useful to centers considering administering gadofosveset trisodium to pediatric patients.

MRI characterization of brown adipose tissue in obese and normal-weight children.

BACKGROUND: Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. OBJECTIVE: To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. MATERIALS AND METHODS: Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. RESULTS: MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). CONCLUSION: This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown adipose tissues between obese and normal-weight children.

Quantitative MRI for hepatic fat fraction and T2* measurement in pediatric patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The gold standard for diagnosis is liver biopsy. MRI is a non-invasive imaging method to provide quantitative measurement of hepatic fat content. The methodology is particularly appealing for the pediatric population because of its rapidity and radiation-free imaging techniques. OBJECTIVE: To develop a multi-point Dixon MRI method with multi-interference models (multi-fat-peak modeling and bi-exponential T2* correction) for accurate hepatic fat fraction (FF) and T2* measurements in pediatric patients with NAFLD. MATERIALS AND METHODS: A phantom study was first performed to validate the accuracy of the MRI fat fraction measurement by comparing it with the chemical fat composition of the ex-vivo pork liver-fat homogenate. The most accurate model determined from the phantom study was used for fat fraction and T2* measurements in 52 children and young adults referred from the pediatric hepatology clinic with suspected or identified NAFLD. Separate T2* values of water (T2*W) and fat (T2*F) components derived from the bi-exponential fitting were evaluated and plotted as a function of fat fraction. In ten patients undergoing liver biopsy, we compared histological analysis of liver fat fraction with MRI fat fraction. RESULTS: In the phantom study the 6-point Dixon with 5-fat-peak, bi-exponential T2* modeling demonstrated the best precision and accuracy in fat fraction measurements compared with other methods. This model was further calibrated with chemical fat fraction and applied in patients, where similar patterns were observed as in the phantom study that conventional 2-point and 3-point Dixon methods underestimated fat fraction compared to the calibrated 6-point 5-fat-peak bi-exponential model (P < 0.0001). With increasing fat fraction, T2*W (27.9 ± 3.5 ms) decreased, whereas T2*F (20.3 ± 5.5 ms) increased; and T2*W and T2*F became increasingly more similar when fat fraction was higher than 15-20%. Histological fat fraction measurements in ten patients were highly correlated with calibrated MRI fat fraction measurements (Pearson correlation coefficient r = 0.90 with P = 0.0004). CONCLUSION: Liver MRI using multi-point Dixon with multi-fat-peak and bi-exponential T2* modeling provided accurate fat quantification in children and young adults with non-alcoholic fatty liver disease and may be used to screen at-risk or affected individuals and to monitor disease progress noninvasively.

Onyx embolization of intracranial arteriovenous malformations in pediatric patients.

OBJECT: The authors undertook this study to assess the safety and efficacy of Onyx embolization in the treatment of intracranial arteriovenous malformations (AVMs) in pediatric patients. METHODS: All pediatric Onyx embolization of intracranial AVM cases performed consecutively at a single children's hospital over a 5-year period were collected and evaluated. RESULTS: Twenty-five patients (mean age 10.5 years) underwent a total of 38 procedures. An aggregate of 56 pedicles were embolized (mean 1.47 per session). The Spetzler-Martin grade was determined in all cases. Onyx embolization resulted in complete obliteration of the AVM in 3 cases (12%) and partial obliteration in 22 cases (88%). A total of 23 patients underwent surgical treatment. The mean preoperative AVM devascularization in these cases was 72%. One patient was treated with radiosurgery following Onyx embolization. Overall, 10 complications occurred in a total of 38 procedures (26.3%). None of the complications resulted in permanent neurological morbidity. The rate of transient neurological complications was 10.5% (4 of 38 procedures) and the rate of transient nonneurological complications was 5.3% (2 of 38 procedures). The remaining 4 complications were clinically silent (rate of 10.5%). There were no procedure-related deaths in this study population. There was no significant difference in patients with and without complications in terms of demographic characteristics, AVM grade, or embolization features (p ≥ 0.2). Deep venous drainage was associated with higher complication rates (p = 0.03). CONCLUSIONS: Onyx utilization is feasible for preoperative or primary embolization in the treatment of pediatric intracranial AVMs; however, the spectrum of complications encountered is broad, and attention must be paid to the technical nuances of and indications for its use to avoid many potential dangerous effects. Although the overall complication rates were higher than expected, all were either clinically silent or had only transient clinical effects. Thus, this experience suggests that Onyx embolization can be performed safely with a low rate of permanent morbidity in pediatric patients harboring these difficult lesions.

Safety and efficacy of onyx embolization for pediatric cranial and spinal vascular lesions and tumors.

BACKGROUND: Although Onyx is widely used to embolize vascular lesions in adults, the safety and efficacy of this liquid embolic agent for use in children are not well studied. OBJECTIVE: To report our experience using Onyx in pediatric patients for a variety of cranial and spinal vascular lesions and tumors to determine its procedural complication rates, types, and clinical consequences and to highlight the indications for and principles of Onyx embolization in pediatric patients. METHODS: All pediatric Onyx embolization cases performed consecutively by the neuroendovascular services at our 2 institutions over a 5-year period were collected retrospectively and analyzed. RESULTS: Over the study period, 105 Onyx embolization procedures were performed in 69 pediatric patients with a mean follow-up of 112 days. Fifty-two patients harbored "primary" vascular lesions (malformations, fistulas, etc), whereas 17 patients had tumors. Complications occurred in 25 of 105 procedures (23.8%) and included ischemic infarct (7), asymptomatic nontarget embolization (4), intracerebral hemorrhage (3), microcatheter-related vessel perforation (3), retained microcatheter (2), cerebral edema (2), dimethyl sulfoxide-induced pulmonary edema (2), facial ischemia (1), and contrast-induced bronchospasm (1). Neurological morbidity occurred transiently after 10 procedures (9.5%) and permanently after 2 procedures (1.9%). There were no procedure-related deaths. Statistical analysis revealed no predictors of complications among the multiple potential risk factors evaluated. CONCLUSION: Our experience suggests that Onyx can be used effectively for embolization of pediatric cranial and spinal vascular lesions and tumors with low permanent morbidity; however, attention must be paid to the technical nuances of and indications for its use to avoid potential complications.

A semiautomatic postprocessing of liver R2* measurement for assessment of liver iron overload.

PURPOSE: The purpose was to propose and evaluate a semiautomatic postprocessing method to measure liver R2(⁎) values in patients with a broad range of liver iron content. MATERIALS AND METHODS: Multiecho gradient echo magnetic resonance images were acquired in patients diagnosed with thalassemia or other types of congenital anemias. Liver R2(⁎) values were measured using a routine manually defined region-of-interest (mROI) method and a semiautomatic (SA) method. In the semiautomatic method, pixelwise (pSA) and averaged (aSA) signal fitting was performed on the segmented liver tissues after hepatic vessel extraction. The pixelwise fitting approach resulted in a liver R2(⁎) map with an overlay of nonfitted pixels associated with noise performance. The following aSA approach derived overall R2(⁎) by fitting the averaged signal intensities of all pixels within the liver ROI excluding vessels and nonfitted pixels. The measurement accuracy and interobserver agreement using mROI and the two semiautomatic approaches (pSA and aSA) were evaluated. RESULTS: In a total of 45 exams with R2(⁎) ranging from 30 to 1500 s(-1), the R2(⁎) measurements using all three methods were overall highly correlated and concordant with each other. R2(⁎) values measured by aSA were consistently higher than those measured by mROI. At lower R2(⁎) (<1000 s(-1)), R2(⁎) values measured by pSA were consistent with aSA but higher than mROI; with increasing R2(⁎), the pSA method became less stable and underestimated R2(⁎) due to increased noise level. The interobserver agreement was higher for the aSA method compared to pSA and mROI. CONCLUSION: The semiautomatic postprocessing method provides a promising tool for reliable liver R2(⁎) measurement with additional information for overall evaluation of iron distribution and measurement confidence. This method may offer the potential of reducing interoperator variability and improving diagnostic confidence in patients with liver iron overload.

Pre- and postoperative imaging and interventions for the meso-Rex bypass in children and young adults.

The meso-Rex bypass is a physiological and anatomical bypass procedure for relief of extrahepatic portal vein obstruction and restoration of mesenteric venous return to the liver. Most patients who are candidates for the bypass are children or young adults with portal hypertension and hypersplenism secondary to cavernous transformation of the portal vein. Most frequently, the bypass utilizes an autologous venous graft to connect the intrahepatic left portal vein to the infrapancreatic superior mesenteric vein (SMV) re-establishing first-pass portal perfusion. We describe the preoperative imaging of the 92 bypass candidates, the surgical anatomy as reflected in postoperative imaging, and the imaging of bypass complications at our institution.Preoperative imaging with US, CT and MR is directed to demonstrate patency and size of the left portal vein and SMV, to define the extent of cavernous transformation and splanchnic collaterals, and to assess for any associated abdominal vascular or solid organ abnormalities. Postoperative imaging is aimed at diagnosing meso-Rex bypass stenosis or occlusion and the interventional management of these complications.