Matthias H. Schmidt

White matter hyperintensities in affected and unaffected late teenage and early adulthood offspring of bipolar parents: A two-center high-risk study

BACKGROUND White matter hyperintensities (WMHs) are among the most replicated neuroimaging findings in bipolar disorder (BD). It is not clear whether these lesions are an artifact of comorbid conditions, or whether they are directly associated with the disorder, or even represent biological risk factor for BD. METHODS To test whether WMHs meet criteria for an endophenotype of BD, we conducted a high-risk design study and recruited 35 affected, 44 unaffected relatives of bipolar probands (age range 15-30 years), matched by age and sex with 49 healthy controls without any personal or family history of psychiatric disorders. The presence of WMHs was determined from Fluid Attenuated Inversion Recovery (FLAIR) scans acquired on a 1.5 Tesla scanner using a validated semi-quantitative scale. RESULTS We found mostly low grade WMHs in all groups. The proportion of WMH-positive subjects was comparable between the unaffected high-risk, affected familial and control groups. CONCLUSION White matter hyperintensities did not meet criteria for an endophenotype of BD. Bipolar disorder in young subjects without comorbid conditions was not associated with increased rate of WMHs.

Lack of response of a metastatic renal perivascular epithelial cell tumor (PEComa) to successive courses of DTIC based‐therapy and imatinib mesylate

An 11 year‐old girl presented with two large abdominal masses in the left flank and epigastrium and left supraclavicular lymphadenopathy. Subsequent investigations led to the diagnosis of metastatic perivascular epithelioid cell tumor (PEComa) arising from the left kidney. Effective treatment for this rare tumor is not yet known. The tumor did not respond to an initial treatment of two cycles of a dacarbazine (DTIC) based regimen. She was placed on a trial of imatinib mesylate based on tumor expression of c‐KIT, a tyrosine kinase targeted by this drug. This report highlights the first documented case of the use of imatinib for PEComa. Lack of response and adverse effects of the drug required discontinuation of therapy.

Sensitivity to White Matter fMRI Activation Increases with Field Strength

Functional magnetic resonance imaging (fMRI) activation in white matter is controversial. Given that many of the studies that report fMRI activation in white matter used high field MRI systems, we investigated the field strength dependence of sensitivity to white matter fMRI activation. In addition, we evaluated the temporal signal to noise ratio (tSNR) of the different tissue types as a function of field strength. Data were acquired during a motor task (finger tapping) at 1.5 T and 4 T. Group and individual level activation results were considered in both the sensorimotor cortex and the posterior limb of the internal capsule. We found that sensitivity increases associated with field strength were greater for white matter than gray matter. The analysis of tSNR suggested that white matter might be less susceptible to increases in physiological noise related to increased field strength. We therefore conclude that high field MRI may be particularly advantageous for fMRI studies aimed at investigating activation in both gray and white matter.

Wavelet-based image registration and segmentation framework for the quantitative evaluation of hydrocephalus

Hydrocephalus, characterized by increased fluid in the cerebral ventricles, is traditionally evaluated by a visual assessment of serial CT scans. The complex shape of the ventricular system makes accurate visual comparison of CT scans difficult. The current research developed a quantitative method to measure the change in cerebral ventricular volume over time. Key elements of the developed framework are: adaptive image registration based on mutual information and wavelet multiresolution analysis; adaptive segmentation with novel feature extraction based on the Dual-Tree Complex Wavelet Transform; volume calculation. The framework, when tested on physical phantoms, had an error of 2.3%. When validated on clinical cases, results showed that cases deemed to be normal/stable had a calculated volume change less than 5%. Those with progressive/treated hydrocephalus had a calculated change greater than 20%. These findings indicate that the framework is reasonable and has potential for development as a tool in the evaluation of hydrocephalus.

Voriconazole treatment of presumptive disseminated Aspergillus infection in a child with acute leukemia.

Invasive fungal infection continues to pose a significant threat to immunocompromised patients. The authors describe a pediatric patient receiving chemotherapy for acute undifferentiated leukemia who developed presumptive Aspergillus species infection disseminated to lung, liver, spleen, and bone. The authors report the successful treatment of this infection with the addition of voriconazole, a triazole antimycotic, to treatment with amphotericin and surgical debridement, in the setting of ongoing intensive chemotherapy.

Selecting and Assessing Quantitative Early Ultrasound Texture Measures for Their Association With Cerebral Palsy

Cerebral palsy (CP) develops as a consequence of white matter damage (WMD) in approximately one out of every 10 very preterm infants. Ultrasound (US) is widely used to screen for a variety of brain injuries in this patient population, but early US often fails to detect WMD. We hypothesized that quantitative texture measures on US images obtained within one week of birth are associated with the subsequent development of CP. In this retrospective study, using images from a variety of US machines, we extracted unique texture measures by means of adaptive processing and high resolution feature enhancement. We did not standardize the images, but used patients as their own controls. We did not remove speckle, as it may contain information. To test our hypothesis, we used the ldquorandom forestrdquo algorithm to create a model. The random forest classifier achieved a 72% match to the health outcome of the patients (CP versus no CP), whereas designating all patients as having CP would have resulted in 53% error. This suggests that quantitative early texture measures contain diagnostic information relevant to the development of CP.

Neuroimaging in epilepsy: The state of the art

Our understanding of epileptogenesis is still limited. Knowledge is increasing with regard to structural and functional changes in chronic stages of epilepsy. At the same time, we have to appreciate that there is a significant lack of such information in new‐onset epilepsy. The First Halifax International Epilepsy Conference tried to fill this gap, focusing on the contribution of advanced neuroimaging in early stages of epilepsy. The following article aims to synthesize the themes that emerged from this meeting. Participants agreed that (1) there is a need for a unified theory of epileptogenesis, addressing the interplay of functional and structural brain changes; (2) neuroimaging reveals widespread brain alterations in epilepsy; (3) advances in neuroimaging challenge the concept of “MRI‐negative” (magnetic resonance imaging negative) focal epilepsy; (4) methodologic limitations and potential confounders must be considered in the translation of innovative imaging approaches to clinical practice; and (5) there is an urgent need for longitudinal studies that begin early in the disease process.

The Therapeutic Misconception: A Threat to Valid Parental Consent for Pediatric Neuroimaging Research

Neuroimaging research has brought major advances to child health and well-being. However, because of the vulnerabilities associated with neurological and developmental conditions, the parental need for hope, and the expectation of parents that new medical advances can benefit their child, pediatric neuroimaging research presents significant challenges to the general problem of consent in the context of research involving children. A particular challenge in this domain is created by the presence of therapeutic misconception on the part of parents and other key research stakeholders. This article reviews the concept of therapeutic misconception and its role in pediatric neuroimaging research. It argues that this misconception can compromise consent given by parents for the involvement of their children in research as healthy controls or as persons with neurological and developmental conditions. The article further contends that therapeutic misconception can undermine the research ethics review process for proposed and ongoing neuroimaging studies. Against this backdrop, the article concludes with recommendations for mitigating the effects of therapeutic misconception in pediatric neuroimaging research.

CT-estimated volume of Wilms tumor can predict weight.

Wilms tumor weight was used to recruit patients in a recent National Wilms Tumor Study (NWTS) group trial. The authors hypothesized that a simple calculation of tumor volume based on a preoperative CT scan could predict tumor weight. The authors reviewed charts and CT images of patients with Wilms tumors who were treated at their institution between 1985 and 2002. Tumor volume was calculated as: V = 1/6π × d (long axis) × d (short axis) × d (craniocaudad). Weight and calculated tumor volume were correlated using linear regression. Complete data of tumor weight and volume could be determined in 25 of the 49 patients. These were highly correlated (Spearman R2 = 0.97). Wilms tumor weight can be predicted based on a simple estimate of tumor volume on a preoperative CT scan. CT-estimated volume may replace weight as a prognostic factor and in guiding management.

High glucose uptake unexpectedly is accompanied by high levels of the mitochondrial β-F1-ATPase subunit in head and neck squamous cell carcinoma

A hallmark of solid tumors is the consumption of large amounts of glucose and production of lactate, also known as Warburg-like metabolism. This metabolic phenotype is typical for aggressive tumor growth, and can be visualized by 18F-fluorodeoxyglucose (18F-FDG) uptake detected by positron emission tomography (PET). High 18F-FDG uptake inversely correlates with survival and goes along with reduced expression of the catalytic beta-subunit of the H+-ATP synthase (β-F1-ATPase) in several tumor entities analyzed so far. For this study we characterized a series of 15 head and neck squamous cell carcinoma (HNSCC) by (i) determining 18F-FDG-uptake; (ii) quantitative expression analysis of β-F1-ATPase (Complex V), NDUF-S1 (Complex I) and COX1 (Complex IV) of the mitochondrial electron transport chain (ETC), as well as Hsp60 (mitochondrial mass) and GAPDH (glycolysis) in tumor cells; (iii) sequencing of the mtDNA of representative tumor samples. Whereas high 18F-FDG-uptake also correlates with poor prognosis in HNSCC, it surprisingly is accompanied by high levels of β-F1-ATPase, but not by any of the other analyzed proteins. In conclusion, we here describe a completely new phenotype of metabolic adaptation possibly enabling those tumors with highest levels of β-F1-ATPase to rapidly proliferate even in hypoxic zones, which are typical for HNSCC.