Ectopic pituitary neuroendocrine tumor arising in the sphenoid sinus with an avid 18F-fluorodeoxyglucose uptake masquerading as malignancy: A case report.

Ectopic pituitary neuroendocrine tumors (PitNETs) are uncommon conditions that develop outside of the sella turcica. The sphenoid sinus is the most common site for ectopic PitNET, followed by the suprasellar region, clivus, and cavernous sinus. PitNETs, regardless of whether inside or outside sella, may display avid 18F-fluorodeoxyglucose (FDG) uptake and masquerade as malignant tumors. Herein, we report a case of ectopic PitNET arising in the sphenoid sinus, which was found as an FDG-avid mass during cancer screening. On magnetic resonance imaging, the tumor showed heterogeneous and intermediate signal intensity areas on T1- and T2-weighted images with cystic components, which was consistent with PitNET. The localization and the presence of empty sella were suggestive of ectopic PitNET, and the diagnosis of ectopic PitNET (prolactinoma) was confirmed by endoscopic biopsy. Ectopic PitNET should be considered in a mass similar in nature to an orthogonal PitNET in areas near the sella turcica especially in patients with empty sella.

Differential diagnosis of thymic epithelial neoplasms on computed tomography using the diameter of the thymic vein.

ABSTRACT: Although differentiating benign and malignant thymic epithelial lesions is important to avoid unnecessary treatment and predict prognosis, it is challenging because of overlaps in the chest computed tomography (CT) findings. In this study, we investigated whether the diameter of the thymic vein and other CT findings could differentiate between benign (thymoma and thymic cysts) and malignant (thymic carcinoma, [TCa]) lesions.We conducted a retrospective study across two tertiary referral hospitals in Japan between November 2009 and June 2018. We included 12 patients with TCa, 34 patients with thymomas, and 17 patients with thymic cysts. We analyzed the receiver operating characteristic (ROC) curve to determine the best cut-off values and performed univariate and multivariate analyses of CT findings to distinguish TCa from other benign lesions. Post-hoc analysis was performed for the maximum short axis of the thymic vein using the Mann-Whitney U test, and the number of the maximum short axis of the thymic vein ≥ the cutoff was determined using the Fisher exact test with a family-wise error-correction using Bonferroni's method.ROC analysis showed that a maximum short axis of the thymic vein ≥2 mm was considerably more frequent in TCa than in the other lesions (P < .001 for both), with 83% sensitivity and 86% specificity. Univariate and multivariate analyses revealed the association with TCa of the number of the maximum short axis of the thymic vein ≥2 mm (P = .005, multivariate generalized linear model analysis), ill-defined margin (P = .001), and mediastinal lymphadenopathy (P < .001). Thymic vein diameter was in descendimg order of TCa > thymoma > thymic cysts with statistically significant differences between the groups (Ps < .05).Thymic vein diameter was significantly longer in TCa than in thymoma and thymic cysts. Measurement of the maximum short axis of the thymic vein could be a powerful diagnostic tool to differentiate TCa from thymoma and thymic cysts.

Long-term survival after pancreatic metastasis resection from breast cancer: a systematic literature review.

BACKGROUND: Patients with advanced-stage breast cancer often demonstrate pancreatic metastases. However, pancreatic metastases resection from breast cancer has been rarely performed, with only 20 cases having been reported to date. CASE PRESENTATION: A 49-year-old woman presented to our hospital in September 2003 with complaints of uncontrollable oozing from her left breast tumor. Computed tomography revealed a left breast tumor approximately 9.3 cm in diameter as well as heterogeneously enhanced solid mass lesions with necrotic foci in the pancreatic tail and body, up to 6.2 cm, which were radiologically diagnosed as pancreatic metastases from breast cancer. An emergent left simple mastectomy was performed to control bleeding. After epirubicin and cyclophosphamide hydrate treatment failed to improve her condition, the pancreatic metastases responded to weekly paclitaxel treatment, but eventually regrew. The patient underwent distal pancreatectomy with splenectomy, left adrenalectomy, partial stomach resection, and paraaortic lymph nodes excision in December 2004 after no other metastasis was confirmed. Furthermore, she received radiation therapy for left parasternal lymph node metastasis 6 months later. The patient recovered well. Consequently, she has no evidence of disease > 15 years after pancreatectomy. CONCLUSIONS: This is the first reported case of pancreatectomy for pancreatic metastases from breast cancer, which was simultaneously diagnosed. Patients with no metastasis other than resectable pancreatic metastases and breast cancer and who possess some sensitivity for chemotherapy may benefit from pancreatectomy.

Cerebral amyloid-ß-related angiitis without cerebral microbleeds in a patient with subarachnoid hemorrhage.

Amyloid-ß-related angiitis (ABRA), a subtype of cerebral amyloid angiopathy (CAA), is vasculitis occurring in relation to amyloid-ß (Aß) deposition in the walls of intracranial blood vessels. ABRA is presumed to be caused by some immune response to the deposited Aß. An 81-year-old man on oral anticoagulant therapy complained of headache, nausea, and difficulty with standing after a head injury. Head computed tomography revealed subcortical bleeding in the right temporoparietal lobe, and 3 days after admission, magnetic resonance imaging (MRI) showed subarachnoid hemorrhage (SAH) around the hematoma. Cerebral microbleeds, a characteristic of CAA, were not detected on MRI. On worsening of his symptoms, intracranial brain biopsy and hematoma removal were performed. Intraoperative rapid diagnosis with a frozen section suspected vasculitis, which enabled the prompt initiation of steroid therapy. He was pathologically diagnosed with ABRA (granulomatous angiitis) using a formalin-fixed paraffin-embedded section. Vasculitis was prominent around blood vessels in the pia matter covering the cerebrum. In this case, the inflammatory cells seemed to appear via the subarachnoid space following cerebral hemorrhage and SAH. ABRA seemed to be developed by intracranial hemorrhage in this case.

Fishbone migration to bile ducts after pancreaticoduodenectomy: a case series.

We reviewed six cases suspected of having fish bones in the bile ducts on follow-up CT following pancreaticoduodenectomy. The period from surgery to CT examination in which fishbone migration was first suspected ranged from 282 to 1157 days with a median of 517 days. The fish bone in the bile duct disappeared in five out of six cases on subsequent CT. One case was complicated by hepatolithiasis, and the other five cases showed no biliary complications. In two cases, wandering of fish bones in the jejunal limb was observed on CT images before their migration into the bile ducts. Asymptomatic migration of fish bones to the bile ducts following pancreaticoduodenectomy is not rare, but serious complications can occasionally occur. Indications of intervention may be controversial in asymptomatic cases, but once fish bones are observed in the biliary tree or the jejunal limb, dietary instructions advising not to swallow fish bones may be a good option to prevent complications.

Altered structural connectivity of pain-related brain network in burning mouth syndrome-investigation by graph analysis of probabilistic tractography.

PURPOSE: Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome featuring idiopathic oral pain and burning discomfort despite clinically normal oral mucosa. The etiology of chronic pain syndrome is unclear, but preliminary neuroimaging research has suggested the alteration of volume, metabolism, blood flow, and diffusion at multiple brain regions. According to the neuromatrix theory of Melzack, pain sense is generated in the brain by the network of multiple pain-related brain regions. Therefore, the alteration of pain-related network is also assumed as an etiology of chronic pain. In this study, we investigated the brain network of BMS brain by using probabilistic tractography and graph analysis. METHODS: Fourteen BMS patients and 14 age-matched healthy controls underwent 1.5T MRI. Structural connectivity was calculated in 83 anatomically defined regions with probabilistic tractography of 60-axis diffusion tensor imaging and 3D T1-weighted imaging. Graph theory network analysis was used to evaluate the brain network at local and global connectivity. RESULTS: In BMS brain, a significant difference of local brain connectivity was recognized at the bilateral rostral anterior cingulate cortex, right medial orbitofrontal cortex, and left pars orbitalis which belong to the medial pain system; however, no significant difference was recognized at the lateral system including the somatic sensory cortex. A strengthened connection of the anterior cingulate cortex and medial prefrontal cortex with the basal ganglia, thalamus, and brain stem was revealed. CONCLUSION: Structural brain network analysis revealed the alteration of the medial system of the pain-related brain network in chronic pain syndrome.

A Japanese, Multicenter, Open-label, Phase 3 Study to Investigate the Safety and Efficacy of Gadobutrol for Contrast-enhanced MR Imaging of the Central Nervous System.

PURPOSE: Gadobutrol 1.0 M is macrocyclic gadolinium-based contrast agent for magnetic resonance imaging (MRI). This multicenter, open-label, phase 3 study aimed to investigate the efficacy and safety of gadobutrol-enhanced versus unenhanced MRI in the visualization and diagnosis of central nervous system (CNS) lesions in Japanese patients. METHODS: A total of 223 patients referred for contrast-enhanced MRI of the CNS underwent unenhanced and gadobutrol-enhanced (0.1 mmol/kg body weight) MRI. The unenhanced and combined (unenhanced and enhanced) images were evaluated by three independent readers in a blinded manner for degree of contrast enhancement, border delineation, internal morphology, and number of detected lesions (primary variables), and for primary diagnosis and diagnostic confidence. Final clinical diagnoses were established by an independent truth committee consisting of two neurosurgeons. Sensitivity, specificity, and accuracy were calculated for the detection of malignancy and the preciseness of diagnoses (secondary variables) by comparing the results obtained by the blinded readers and the truth committee. RESULTS: Gadobutrol enhancement significantly improved three visualization parameters in MR images: contrast enhancement, border delineation, and internal morphology (P < 0.0001). Non-inferiority was achieved for mean number of lesions detected. Gadobutrol-enhanced imaging provided significant improvements in sensitivity and accuracy for the detection of malignant disease with no loss in specificity, and also improvements in accuracy of exact match diagnosis and diagnostic confidence. Drug-related adverse events were reported in 6 out of 223 patients (2.7%); all were non-serious. CONCLUSION: Gadobutrol is an effective and well-tolerated contrast agent for MR imaging of the CNS.

Efficacy of distortion correction on diffusion imaging: comparison of FSL eddy and eddy_correct using 30 and 60 directions diffusion encoding.

Diffusion imaging is a unique noninvasive tool to detect brain white matter trajectory and integrity in vivo. However, this technique suffers from spatial distortion and signal pileup or dropout originating from local susceptibility gradients and eddy currents. Although there are several methods to mitigate these problems, most techniques can be applicable either to susceptibility or eddy-current induced distortion alone with a few exceptions. The present study compared the correction efficiency of FSL tools, "eddy_correct" and the combination of "eddy" and "topup" in terms of diffusion-derived fractional anisotropy (FA). The brain diffusion images were acquired from 10 healthy subjects using 30 and 60 directions encoding schemes based on the electrostatic repulsive forces. For the 30 directions encoding, 2 sets of diffusion images were acquired with the same parameters, except for the phase-encode blips which had opposing polarities along the anteroposterior direction. For the 60 directions encoding, non-diffusion-weighted and diffusion-weighted images were obtained with forward phase-encoding blips and non-diffusion-weighted images with the same parameter, except for the phase-encode blips, which had opposing polarities. FA images without and with distortion correction were compared in a voxel-wise manner with tract-based spatial statistics. We showed that images corrected with eddy and topup possessed higher FA values than images uncorrected and corrected with eddy_correct with trilinear (FSL default setting) or spline interpolation in most white matter skeletons, using both encoding schemes. Furthermore, the 60 directions encoding scheme was superior as measured by increased FA values to the 30 directions encoding scheme, despite comparable acquisition time. This study supports the combination of eddy and topup as a superior correction tool in diffusion imaging rather than the eddy_correct tool, especially with trilinear interpolation, using 60 directions encoding scheme.

Detection of lung tumors in mice using a 1-tesla compact magnetic resonance imaging system.

Due to their small size, lung tumors in rodents are typically investigated using high-field magnetic resonance (MR) systems (4.7 T or higher) to achieve higher signal-to-noise ratios, although low-field MR systems are less sensitive to susceptibility artifacts caused by air in the lung. We investigated the feasibility of detecting lung tumors in living, freely breathing mice with a 1-T compact permanent magnet MR system. In total, 4 mice were used, and MR images of mouse lungs were acquired using a T1-weighted three-dimensional fast low-angle shot sequence without cardiac or respiratory gating. The delineation and size of lung tumors were assessed and compared with histopathological findings. Submillimeter lesions were demonstrated as hyperintense, relative to the surrounding lung parenchyma, and were delineated clearly. Among the 13 lesions validated in histopathological sections, 11 were detected in MR images; the MR detection rate was thus 84.6%. A strong correlation was obtained in size measurements between MR images and histological sections. Thus, a dedicated low-field MR system can be used to detect lung tumors in living mice noninvasively without gating.

Erdheim-Chester disease with an 18F-fluorodeoxyglucose-avid breast mass and BRAF V600E mutation.

Erdheim-Chester disease (ECD) is a non-Langerhans cell histiocytosis. Herein we report a case of a 49-year-old woman who developed bilateral knee pain. Imaging procedures revealed multiple long bone lesions and a well-defined 18F-fluorodeoxyglucose-avid mass in the left breast. The breast mass was resected, and an open biopsy was performed on the right femoral lesion. Both specimens revealed involvement by histiocytic infiltrates with features suggestive of ECD. The BRAF V600E mutation was detected by DNA sequencing and immunohistochemistry.

Tract-specific analysis of white matter integrity disruption in schizophrenia.

Several studies have suggested that white matter integrity is disrupted in some brain regions in patients with schizophrenia. The purpose of this study was to assess the white matter integrity of the cingulum, uncinate fasciculus, fornix, and corpus callosum using diffusion tensor imaging (DTI). Participants comprised 39 patients with schizophrenia (19 males and 20 females) and 40 age-matched normal controls (20 males and 20 females). We quantitatively assessed the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the anterior cingulum, body of the cingulum, uncinate fasciculus, fornix, and corpus callosum on a tract-specific basis using diffusion tensor tractography (DTT). Group differences in FA and ADC between the patients and normal controls were sought. Additional exploratory analyses of the relationship between the FA or ADC and four clinical parameters (i.e., illness duration, positive symptom scores, negative symptom scores, and medication dosage) were performed. Results were analyzed in gender-combined and gender-separated group comparisons. FA was significantly lower on both sides of the anterior cingulum, uncinate fasciculus, and fornix in the schizophrenia patients irrespective of gender group separation. In the gender-combined analyses, significantly higher ADC values were demonstrated in the schizophrenia patients in both sides of the anterior cingulum, body of the cingulum and uncinate fasciculus, the left fornix, and the corpus callosum, compared with those of the normal controls. In the gender-separated analyses, the male patients showed higher ADC in the left anterior cingulum, the bilateral cingulum bodies, and the bilateral uncinate fasciculi. The female patients showed higher ADC in the right anterior cingulum, the left fornix, and the bilateral uncinate fasciculus. In correlation analyses, a significant negative correlation was found between illness duration and ADC in the right anterior cingulum in the gender-combined analyses. The gender-separated analyses found that the male patients had a significant negative correlation between negative symptom scores and FA in the right fornix, a positive correlation between illness duration and FA in the right anterior cingulum, and a negative correlation between illness duration and FA in the left uncinate fasciculus. Our DTI study showed that the integrity of white matter is disrupted in patients with schizophrenia. The results of our sub-analyses suggest that changes in FA and ADC may be related to negative symptom scores or illness duration.

Association between the oxytocin receptor gene and amygdalar volume in healthy adults.

BACKGROUND: Recent studies have suggested that oxytocin affects social cognition and behavior mediated by the oxytocin receptor (OXTR) in amygdala in humans as well as in experimental animals. Genetic studies have revealed a link between the OXTR gene and the susceptibility to autism spectrum disorders (ASD), especially in the social dysfunctional feature of ASD. METHODS: We examined the relationship between amygdala volume measured with manual tracing methodology and seven single nucleotide polymorphisms and one haplotype-block in OXTR, which were previously reported to be associated with ASD, in 208 socially intact Japanese adults with no neuropsychiatric history or current diagnosis. RESULTS: The rs2254298A allele of OXTR was significantly associated with larger bilateral amygdala volume. The rs2254298A allele effect on amygdala volume varied in proportion to the dose of this allele. The larger the number of rs2254298A alleles an individual had, the larger their amygdala volume. Such an association was not observed with hippocampal volume or with global brain volumes, including whole gray, white matter, and cerebrospinal-fluid space. Furthermore, two three-single nucleotide polymorphism haplotypes, including rs2254298G allele, showed significant associations with the smaller bilateral amygdala volume. CONCLUSIONS: The present results suggest that OXTR might be associated with the susceptibility to ASD, especially in its aspects of social interaction and communication mediated by a modulation of amygdala development, one of the most distributed brain regions with high density of OXTR. Furthermore, amygdala volume measured with magnetic resonance imaging could be a useful intermediate phenotype to uncover the complex link between OXTR and social dysfunction in ASD.

Reduced gray matter volume of pars opercularis is associated with impaired social communication in high-functioning autism spectrum disorders.

BACKGROUND: Recent literature suggests that the inferior frontal gyrus, especially its posterior portion, has an important role in imitation and social reciprocity and in the pathophysiology of their disturbance in autism spectrum disorders (ASD). However, the structural abnormality of this region has not fully been clarified in subjects with ASD. METHODS: Here we obtained magnetic resonance images from 13 right-handed men with high-functioning ASD (Asperger disorder [n = 10] or autism [n = 3]) and from 11 age-, parental socioeconomic background-, and intelligence quotient-matched right-handed typical men. A reliable manual tracing methodology was employed to measure the gray matter volume of the pars opercularis, corresponding to Brodmann area 44, and the pars triangularis, corresponding to Brodmann area 45. RESULTS: A significant gray matter volume reduction of both the pars opercularis and triangularis was found bilaterally in the subjects with ASD compared with the typical control subjects. The effect size seemed to be larger for pars opercularis (1.25) than for pars triangularis (.90). The reduced volume of right as well as total pars opercularis showed a significant association with the increased severity of social communication problems in the ASD group. CONCLUSIONS: The current findings support an important role of pars opercularis, a center of the mirror neuron system, in the pathophysiology of ASD.

Voxel-based analysis of the diffusion tensor.

INTRODUCTION: Diffusion tensor imaging (DTI) has provided important insights into the neurobiological basis for normal development and aging and various disease processes in the central nervous system. The aim of this article is to review the current protocols for DTI acquisition and preprocessing and statistical testing for a voxelwise analysis of DTI, focused on statistical parametric mapping (SPM) and tract-based spatial statistics (TBSS). METHODS: We tested the effects of distortion correction induced by gradient nonlinearity on fractional anisotropy (FA) maps or FA skeletons processed via two SPM-based methods (coregistration and FA template methods), or TBSS-based method, respectively. RESULTS: With two SPM-based methods, we found similar results in some points (e.g., significant FA elevation for uncorrected images in anterior-dominant white matter and for corrected images in bilateral middle cerebellar peduncles) and different results in other points (e.g., significantly larger FA for corrected images with coregistration method, but significantly smaller with FA template method in bilateral internal capsules, extending to corona radiata, and semioval centers). In contrast, there was no area with significant difference between uncorrected and corrected FA skeletons with TBSS-based method. CONCLUSION: The discrepancy among these results was not explained in full, but possible explanations were misregistration and smoothing for the SPM-based methods and insensitivity to FA changes outside the local centers of white matter bundles for TBSS-based method.

Endometrial stromal sarcoma located in the myometrium with a low-intensity rim on T2-weighted images: report of three cases and literature review.

Endometrial stromal sarcoma (ESS) most commonly grows from the uterine endometrium into the endometrial cavity; it is rarely located in the myometrium alone, where it may resemble degenerated leiomyoma on magnetic resonance imaging (MRI). We present three cases of intramyometrial ESS mimicking degenerated leiomyoma, all of which have a characteristic low-intensity rim on T2-weighted images. Histopathological examination revealed the rim to consist of fibrous tissue layers and/or a decrease in free water caused by distortion of myometrial tissue following tumor expansion. ESS should be included in the differential diagnosis of intramyometrial mass with low-intensity rim on T2-weighted image, especially if the mass shows degeneration with no or mild intratumoral hemorrhage.

Sex dimorphism in gray/white matter volume and diffusion tensor during normal aging.

The purpose of this study is to elucidate sex differences in global and regional gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) during normal aging using voxel-based analysis. We studied 245 healthy right-handed subjects with a wide range of ages (115 women, 22-70 years; 130 men, 21-71 years). Regarding global effects, inclusion of a quadratic age term improved the fit to data for white matter fraction and MD, but not for global gray matter volume/fraction or FA. Regarding regional effects, we found anterior-dominant volume loss, FA decrease predominantly in the anterior white matter, and MD increase predominantly in perisylvian regions and periventricular white matter against age for both sexes. Compared with women, we found a steeper FA decline for men in the right inferior fronto-temporal areas, extending to the anterior cingulate cortex, and an accelerated MD increase for men in the bilateral frontal, temporal, and parietal areas. There was no area in which interaction of sex with age was significant for regional volume, or in which a steeper FA decline or accelerated MD increase for women was significant. Our results provide strong evidence of sex dimorphism in global and focal diffusion characteristics during normal aging.

Effect of tryptophan hydroxylase-2 gene variants on amygdalar and hippocampal volumes.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin (5-HT). Genetic variations in human TPH2, a newly identified isoform of TPH, have been shown to impact on enzymatic activity of TPH and to be associated with emotion-related personality traits and mood/anxiety disorders. Identification of an intermediate phenotype that bridges the relationship between genes and behavior may be of great importance in the further clarification of how hTPH2 contributes to emotional regulation. Previous studies have shown that a polymorphism in the upstream regulatory region of hTPH2 (SNP G-703T, rs4570625) correlates functional MRI response of the amygdala. In this study, we examined the effect of this genotype on amygdalar and hippocampal volumes in 208 mentally healthy individuals. To measure volumes of amygdala and hippocampus, gray matter regions of interest were outlined manually on three-dimensional MRI data obtained using a 1.5-T scanner. Additionally, personality traits were evaluated using the Temperament and Character Inventory (TCI). Those subjects with T allele carriers were associated with significantly smaller volumes in bilateral amygdala and hippocampus and higher reward dependence than those with G allele homozygotes. These results suggest that amygdalar and hippocampal volumes assessed using MRI may be a useful intermediate phenotype that will uncover the biological pathway linking 5-HT synthesis and emotional behaviors and affective disorders.

A case of adult-onset type II citrullinemia with comorbid epilepsy even after liver transplantation.

The current study using single case voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) and ¹H-MR-spectroscopy (¹H-MRS) explores the neural background of unexplained seizure attacks and electroencephalography (EEG) abnormalities persisting even after liver transplantation in a patient with adult-onset type II citrullinemia (CTLN2). Although the MRI had shown no gross abnormality, the VBM revealed significantly smaller-than-normal regional volume in the left hippocampus of the patient as compared with 111 age-matched controls. ¹H-MRS further indicated reduction of all metabolite concentrations in the left hippocampus compared with those in the right homolog region, with the single exception of elevated glutamate concentration. These results are similar to those of patients with mesial temporal lobe epilepsy (TLE), although CTLN2-complicated mesial TLE has rarely been reported. In contrast to TLE, periictal asterixis and interictal slow activities on EEG support another possibility that the patient might have slight metabolic encephalopathy even after the liver transplantation.

Age-related changes in regional brain volume evaluated by atlas-based method.

INTRODUCTION: The effects of aging on brain volume are generally investigated using voxel-based morphometry (VBM) or the manually traced region-of-interest (ROI) method. We introduce an atlas-based method as a methodological alternative that calculates absolute volume as a non-biased and semi-automatic whole-brain technique. METHODS: We enrolled 115 healthy females (mean age, 36.7 years) and 130 healthy males (mean age, 37.1 years). Volume data were acquired using a 1.5 tesla magnetic resonance scanner. After spatial normalization, a lobar-based atlas template was applied, and the absolute volumes of the frontal, temporal, parietal, and occipital lobes and the sublobar and limbic areas were calculated bilaterally. The effects of age on regional brain volume were evaluated statistically. RESULTS: The volume of all ROIs declined linearly with increasing age. The bilateral frontal lobes showed the steepest involution. Analysis of variance revealed significant laterality and interaction of gender and age. CONCLUSION: The atlas-based method introduced in the present study has advantages over the manually traced ROI method in its objectivity, coverage, and time requirement and has an advantage over the VBM method in its computability of absolute volume. The results are largely in agreement with those reported previously, thereby reconfirming the importance of matching gender and age in analyzing brain disorders.

Reduced gray matter volume of Brodmann's Area 45 is associated with severe psychotic symptoms in patients with schizophrenia.

Previous literature has suggested an important role of inferior frontal gyrus, which mainly consists of Brodmann's Area (BA) 44 and 45, in the pathophysiology of schizophrenia. While recent neuroimaging techniques have revealed differential functional correlates of BA 44 and 45 in healthy individuals, previous studies have not yet separately evaluated the gray matter volume reduction of BA 44 and 45 and their relationships to psychotic symptoms in patients with schizophrenia. In the present study, magnetic resonance images were obtained from 29 right-handed male patients with schizophrenia and from 29 age- and handedness-matched healthy male controls. The reliable manual tracing methodology was employed to measure the gray matter volume of BA 44 and BA 45. The severities of psychotic symptoms were evaluated using the five-factor model of positive and negative syndrome scale in the patient group. A significant gray matter volume reduction of both the BA 44 and BA 45 was found bilaterally in the patients with schizophrenia compared with the healthy controls. Among these inferior frontal sub-regions, reduced volume of right BA 45 revealed the largest effect size. In addition, the reduced volume of BA 45 in left hemisphere showed a significant association with the increased severity of delusional behavior, while the severity of disorganized and positive symptoms were correlated with the bilateral BA 45 volumes in the patient group. The findings support an important role of inferior frontal gyrus in the pathophysiology of schizophrenia. The present study further demonstrated that BA 45 might especially contribute to the production of psychotic symptoms in the patients with schizophrenia.