Per H. Nakstad

Cortical Thickness and Subcortical Volumes in Schizophrenia and Bipolar Disorder

BACKGROUND Schizophrenia and bipolar disorder are severe psychiatric diseases with overlapping symptomatology. Widespread brain morphologic abnormalities, including cortical thinning and subcortical volume reductions, have been demonstrated in schizophrenia but it is unclear whether similar abnormalities are present in bipolar disorder. The purpose of this study was to compare cortical thickness and subcortical volumes in schizophrenia and bipolar disorder, to assess differences and similarities in cortical and subcortical brain structure. METHODS We analyzed magnetic resonance images from a sample of 173 patients with schizophrenia spectrum disorder, 139 patients with bipolar disorder, and 207 healthy control subjects. Cortical thickness was compared between the groups in multiple locations across the continuous cortical surface. Subcortical volumes were compared on a structure-by-structure basis. RESULTS There was widespread cortical thinning in schizophrenia compared with control subjects, in frontal, temporal, occipital, and smaller parietal regions. There was no cortical thinning in bipolar disorder compared with control subjects or in schizophrenia compared with bipolar disorder. However, the subgroup of patients with bipolar disorder Type 1 showed cortical thinning, primarily in the frontal lobes and superior temporal and temporoparietal regions. Both patient groups showed substantial subcortical volume reductions bilaterally in the hippocampus, the left thalamus, the right nucleus accumbens, the left cerebellar cortex, and the brainstem, along with substantial ventricular enlargements. CONCLUSIONS We found substantial overlap in the underlying brain morphologic abnormalities in schizophrenia and bipolar disorder in subcortical structures, and between schizophrenia and bipolar disorder Type 1 in the cerebral cortex.

THE HUMAN AMYGDALA IS INVOLVED IN GENERAL BEHAVIORAL RELEVANCE DETECTION: EVIDENCE FROM AN EVENT-RELATED FUNCTIONAL MAGNETIC RESONANCE IMAGING Go-NoGo TASK

The amygdala is classically regarded as a detector of potential threat and as a critical component of the neural circuitry mediating conditioned fear responses. However, it has been reported that the human amygdala responds to multiple expressions of emotions as well as emotionally neutral stimuli of a novel, uncertain or ambiguous nature. Thus, it has been proposed that the function of the amygdala may be of a more general art, i.e. as a detector of behaviorally relevant stimuli [Sander D, Grafman J, Zalla T (2003) The human amygdala: an evolved system for relevance detection. Rev Neurosci 14:303-316]. To investigate this putative function of the amygdala, we used event related functional magnetic resonance imaging (fMRI) and a modified Go-NoGo task composed of behaviorally relevant and irrelevant letter and number stimuli. Analyses revealed bilateral amygdala activation in response to letter stimuli that were behaviorally relevant as compared with letters with less behavioral relevance. Similar results were obtained for relatively infrequent NoGo relevant stimuli as compared with more frequent Go stimuli. Our findings support a role for the human amygdala in general detection of behaviorally relevant stimuli.

Proton magnetic resonance spectroscopy in the distinction of high-grade cerebral gliomas from single metastatic brain tumors.

Background: Brain metastases and primary high-grade gliomas, including glioblastomas multiforme (GBM) and anaplastic astrocytomas (AA), may be indistinguishable by conventional magnetic resonance (MR) imaging. Identification of these tumors may have therapeutic consequences. Purpose: To assess the value of MR spectroscopy (MRS) using short and intermediate echo time (TE) in differentiating solitary brain metastases and high-grade gliomas on the basis of differences in metabolite ratios in the intratumoral and peritumoral region. Material and Methods: We performed MR imaging and MRS in 73 patients with histologically verified intraaxial brain tumors: 53 patients with high-grade gliomas (34 GBM and 19 AA) and 20 patients with metastatic brain tumors. The metabolite ratios of Cho/Cr, Cho/NAA, and NAA/Cr at intermediate TE and the presence of lipids at short TE were assessed from spectral maps in the tumoral core, peritumoral edema, and contralateral normal-appearing white matter. The differences in the metabolite ratios between high-grade gliomas/GBM/AA and metastases were analyzed statistically. Cutoff values of Cho/Cr, Cho/NAA, and NAA/Cr ratios in the peritumoral edema, as well as Cho/Cr and NAA/Cr ratios in the tumoral core for distinguishing high-grade gliomas/GBM/AA from metastases were determined by receiver operating characteristic (ROC) curve analysis. Results: Significant differences were noted in the peritumoral Cho/Cr, Cho/NAA, and NAA/ Cr ratios between high-grade gliomas/GBM/AA and metastases. ROC analysis demonstrated a cutoff value of 1.24 for peritumoral Cho/Cr ratio to provide sensitivity, specificity, positive (PPV), and negative predictive values (NPV) of 100%, 88.9%, 80.0%, and 100%, respectively, for discrimination between high-grade gliomas and metastases. By using a cutoff value of 1.11 for peritumoral Cho/NAA ratio, the sensitivity was 100%, the specificity was 91.1%, the PPV was 83.3%, and the NPV was 100%. Conclusion: The results of this study demonstrate that MRS can differentiate high-grade gliomas from metastases, especially with peritumoral measurements, supporting the hypothesis that MRS can detect infiltration of tumor cells in the peritumoral edema.

Measurements of diagnostic examination performance using quantitative apparent diffusion coefficient and proton MR spectroscopic imaging in the preoperative evaluation of tumor grade in cerebral gliomas.

PURPOSE Tumor grading is very important both in treatment decision and evaluation of prognosis. While tissue samples are obtained as part of most therapeutic approaches, factors that may result in inaccurate grading due to sampling error (namely, heterogeneity in tissue sampling, as well as tumor-grade heterogeneity within the same tumor specimen), have led to a desire to use imaging better to ascertain tumor grade. The purpose in our study was to evaluate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC), and accuracy of diffusion-weighted MR imaging (DWI), proton MR spectroscopic imaging (MRSI) or both in grading primary cerebral gliomas. MATERIALS AND METHODS We performed conventional MR imaging (MR), DWI, and MRSI in 74 patients with newly diagnosed brain gliomas: 59 patients had histologically verified high-grade gliomas: 37 glioblastomas multiform (GBM) and 22 anaplastic astrocytomas (AA), and 15 patients had low-grade gliomas. Apparent diffusion coefficient (ADC) values of tumor and peritumoral edema, and ADC ratios (ADC in tumor or peritumoral edema to ADC of contralateral white matter, as well as ADC in tumor to ADC in peritumoral edema) were determined from three regions of interest. The average of the mean, maximum, and minimum for ADC variables was calculated for each patient. The metabolite ratios of Cho/Cr and Cho/NAA at intermediate TE were assessed from spectral maps in the solid portion of tumor, peritumoral edema and contralateral normal-appearing white matter. Tumor grade determined with the two methods was then compared with that from histopathologic grading. Logistic regression and receiver operating characteristic (ROC) curve analysis were performed to determine optimum thresholds for tumor grading. Measures of diagnostic examination performance, such as sensitivity, specificity, PPV, NPV, AUC, and accuracy for identifying high-grade gliomas were also calculated. RESULTS Statistical analysis demonstrated a threshold minimum ADC tumor value of 1.07 to provide sensitivity, specificity, PPV, and NPV of 79.7%, 60.0%, 88.7%, and 42.9% respectively, in determining high-grade gliomas. Threshold values of 1.35 and 1.78 for peritumoral Cho/Cr and Cho/NAA metabolite ratios resulted in sensitivity, specificity, PPV, and NPV of 83.3%, 85.1%, 41.7%, 97.6%, and 100%, 57.4%, 23.1% and 100% respectively for determining high-grade gliomas. Significant differences were noted in the ADC tumor values and ratios, peritumoral Cho/Cr and Cho/NAA metabolite ratios, and tumoral Cho/NAA ratio between low- and high-grade gliomas. The combination of mean ADC tumor value, maximum ADC tumor ratio, peritumoral Cho/Cr and Cho/NAA metabolite ratios resulted in sensitivity, specificity, PPV, and NPV of 91.5%, 100%, 100% and 60% respectively. CONCLUSION Combining DWI and MRSI increases the accuracy of preoperative imaging in the determination of glioma grade. MRSI had superior diagnostic performance in predicting glioma grade compared with DWI alone. The predictive values are helpful in the clinical decision-making process to evaluate the histologic grade of tumors, and provide a means of guiding treatment.

Associations Between Variants Near a Monoaminergic Pathways Gene (PHOX2B) and Amygdala Reactivity: A Genome-Wide Functional Imaging Study

As the amygdala is part of the phylogenetic old brain, and its anatomical and functional properties are conserved across species, it is reasonable to assume genetic influence on its activity. A large corpus of candidate gene studies indicate that individual differences in amygdala activity may be caused by genetic variants within monoaminergic signaling pathways such as dopamine, serotonin, and norepinephrine. However, to our knowledge, the use of genome-wide data to discover genetic variants underlying individual differences in adult amygdala activity is novel. In the present study, the combination of genome-wide data and functional imaging phenotypes from an emotional faces task yielded a significant association between rs10014254 and the amygdala using a region of interest approach. This single nucleotide polymorphism is located in a regulatory region upstream of the Paired-like homeobox 2b (PHOX2B) gene; therefore it could affect the expression of this gene. PHOX2B regulates the expression of enzymes necessary for the synthesis of several monoamines and is essential for the development of the autonomic nervous system. However, an attempt to replicate the finding in an independent sample from North America did not succeed. The synthesis of functional magnetic resonance imaging (fMRI) and genome-wide data takes a hypothesis-free approach as to which genetic variants are of interest. Therefore, we believe that an undirected finding within such a plausible region is of interest, and that our results add further support to the hypothesis that monoaminergic signaling pathways play a central role in regulating amygdala activity.

Analysis of diffusion tensor imaging metrics for gliomas grading at 3 T

OBJECTIVES To assess the diagnostic accuracy of axial diffusivity (AD), radial diffusivity (RD), apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values derived from DTI for grading of glial tumors, and to estimate the correlation between DTI parameters and tumor grades. METHODS Seventy-eight patients with glial tumors underwent DTI. AD, RD, ADC and FA values of tumor, peritumoral edema and contralateral normal-appearing white matter (NAWM) and AD, RD, ADC and FA ratios: lowest average AD, RD, ADC and FA values in tumor or peritumoral edema to AD, RD, ADC and FA of NAWM were calculated. DTI parameters and tumor grades were analyzed statistically and with Pearson correlation. Receiver operating characteristic (ROC) curve analysis was also performed. RESULTS The differences in ADC, AD and RD tumor values, and ADC and RD tumor ratios were statistically significant between grades II and III, grades II and IV, and between grades II and III-IV. The AD tumor ratio differed significantly among all tumor grades. Tumor ADC, AD, RD and glial tumor grades were strongly correlated. In the ROC curve analysis, the area under the curve (AUC) of the parameter tumor ADC was the largest for distinguishing grade II from grades III to IV (98.5%), grade II from grade IV (98.9%) and grade II from grade III (97.0%). CONCLUSION ADC, RD and AD are useful DTI parameters for differentiation between low- and high-grade gliomas with a diagnostic accuracy of more than 90%. Our study revealed a good inverse correlation between ADC, RD, AD and WHO grades II-IV astrocytic tumors.

Traumatic cervical injuries in ankylosing spondylitis

Purpose: To demonstrate the importance of magnetic resonance (MR) and computed tomography (CT) in the evaluation of cervical traumas in patients suffering from ankylosing spondylitis. Material and Methods: Eleven patients with advanced ankylosing spondylitis were admitted to neurosurgical treatment after trauma to the neck region. All had neurological symptoms and were evaluated with plain X‐ray, CT, and MR. Results: CT with reformation sagittal and coronal plane was superior to plain X‐ray films in demonstrating fractures and dislocations. MR was considered mandatory when evaluating changes in medulla and epidural hematomas, which were detected in 4 patients. The clinical outcome was poor in 5 patients and good in 6. The poorest outcome was seen in patients with cord contusion and epidural hematoma. Conclusion: We conclude that plain X‐ray is of no greater importance in the acute phase of highest value in follow‐up evaluation of the healing process and final position of the fractured vertebrae. Our protocol in the acute phase in traumatized ankylopoetic patients consists of lateral conventional X‐ray, CT with reformatted images, and MR, the last‐mentioned being important in detecting epidural hematoma that reduces the clinical outcome further if not removed. In our opinion, MR must be part of the radiological protocol following neck traumas in all patients with ankylosing spondylitis.

Arousal Modulates Activity in the Medial Temporal Lobe during a Short-Term Relational Memory Task.

This study investigated the effect of arousal on short-term relational memory and its underlying cortical network. Seventeen healthy participants performed a picture by location, short-term relational memory task using emotional pictures. Functional magnetic resonance imaging was used to measure the blood-oxygenation-level dependent signal relative to task. Subjects’ own ratings of the pictures were used to obtain subjective arousal ratings. Subjective arousal was found to have a dose-dependent effect on activations in the prefrontal cortex, amygdala, hippocampus, and in higher order visual areas. Serial position analyses showed that high arousal trials produced a stronger primacy and recency effect than low arousal trials. The results indicate that short-term relational memory may be facilitated by arousal and that this may be modulated by a dose–response function in arousal-driven neuronal regions.

Gender differences in the human brain

Scientific documentation of gender differences in the brain and spinal cord has in the past been difficult to find. In the last decennium the development of magnetic resonance imaging (MRI) and positron emission tomography (PET) has changed this, and continuous increase in knowledge about this field is evolving (1–11). Scientists have, of course, been aware of the existence of complicated brain networks, but lacking the full understanding of how these networks function. Nowadays, combining different methods of imaging, data processing, statistics, and physics creates the possibility to describe and construct understandable brain networks, such as the brain metabolic network described in the study from Nanjing University, China by Yuxiao Hu et al. (12) in this issue of Acta Radiologica. They have used FDG-PET in a material consisting of 400 ethnic Chinese people, 200 women and 200 men. The present paper demonstrates the complexities of studies dealing with these methods in disclosing brain structures and functions. Data processing, statistical methods, mathematics, and physics often play an important role in achieving safe results in such scientific studies. For practical benefit of radiologists and others, hence one objective for this journal, the content of complex studies such as this by Hu et al. may be difficult to fully understand and to gain benefit from. However, as a radiological journal it is one of our obligations as well to present how combinations of new and older methods may increase knowledge in the medical profession, and in particular radiology. This paper opens up a delicate field: anatomical and structural differences between male and female. It might even be difficult for some of us to accept that the female brain topography in some respects is different from that of male brains. The authors show that in women some hubs in the brain have greater gray matter volume and cortical thickness than in men. A few brain regions show significant gender differences in nodal topological metrics. The authors use young individuals in their evaluation, but as pointed out by the authors, one can see many interesting study projects emerging from systematical comparisons between genders, among them changes in the topological parameters during aging (1). Some papers are published regarding gender differences in gray matter (2–7), but regarding the organization of brain networks relatively few papers are published (8–11). The combination of data processing, mathematics, et cetera with modern imaging methods such as MRI and PET opens up a great possibility for important research by colleagues working in the imaging field.

Imaging of Traumatic Brain InjuryAnzaiY, FinkKR (eds.), Imaging of Traumatic Brain Injury, Thieme: New York, 2015; 200 pp.: ISBN 978-1-60406-729-3,

In addition to the two editors, 13 radiologists have contributed to the content. Seven of the 15 contributors are neuroradiologists. Despite the lack of clinical experts the clinical information accompanying the many very instructive images is good and highly relevant. The two first chapters about epidemiology and evidence-based imaging of brain traumas are especially appreciated. Although the epidemiological information mainly refers to conditions in the USA, it is most probably valid for most European and Asian countries as well. However, a comparison with other parts of the world would have been appreciated. The chapters dealing with ‘‘Abusive Head Trauma (Nonaccidental Head Trauma)’’ are important. This topic might probably have deserved a separate, larger chapter. In many regions of the world maltreatment of children has little focus. When dealing with traumatic subarachnoid hemorrhage (tSAH) in the chapters ‘‘Neuroimaging of Traumatic Brain Injury’’ and ‘‘Scull-Base Trauma’’, as well as in ‘‘Arterial Injury’’, traumatic, intracranial, arterial aneurysms are briefly mentioned and no references are given to international literature. Life-threatening traumatic aneurysms might be present when a post-traumatic SAH occurs. Apart from this discrete criticism, the book presents an important contribution to increasing the knowledge of imaging in traumatic brain injury. The illustrations are of high quality and enhance the understanding of the radiological images. In the interesting chapter of evidence-based imaging, the authors present different consensual criteria justifying CT in minor traumatic brain injury patients. The handling of minor head traumas is to some extent disputed and it is therefore understandable that no recommendation is presented; it remains unclear which criteria are followed in the authors’ own institution, Harborview Medical Centre, University of Washington, Seattle. The role of MRI in acute traumatic brain injury is presented. The authors state that no relevance, whether routine detection of lesions (axonal shear injury, extraaxial hematomas) by MRI, will result in improved prognosis or long-term neuro-psychological abnormalities. This might be debated and a reference or two to some European colleague that uses MRI in acute TBI would have been appreciated. The title of the book, Imaging of Traumatic Brain Injury, does not indicate that ‘‘Maxillofacial Trauma’’ and ‘‘Traumatic Orbital and Ocular Injury’’ are dealt with over two chapters. These chapters are extremely well written and relevant cases are extensively presented. It would have been justified to have a title that pointed out these themes as well, not just the brain. The book is organized well and it is easy to use as a reference work. Following each chapter, a comprehensive reference list is given. This enables the reader to dive further into a special topic of interest. I recommend that neuroradiologists and radiologists, as well as all other colleagues working with neurological imaging, have this book on their desk. The book is very well suited for younger colleagues and students as well.