The emergence of dyslexia in the developing brain.

Developmental dyslexia, a severe deficit in literacy learning, is a neurodevelopmental learning disorder. Yet, it is not clear whether existing neurobiological accounts of dyslexia capture potential predispositions of the deficit or consequences of reduced reading experience. Here, we longitudinally followed 32 children from preliterate to school age using functional and structural magnetic resonance imaging techniques. Based on standardised and age-normed reading and spelling tests administered at school age, children were classified as 16 dyslexic participants and 16 controls. This longitudinal design allowed us to disentangle possible neurobiological predispositions for developing dyslexia from effects of individual differences in literacy experience. In our sample, the disorder can be predicted already before literacy learning from auditory cortex gyrification and aberrant downstream connectivity within the speech processing system. These results provide evidence for the notion that dyslexia may originate from an atypical maturation of the speech network that precedes literacy instruction.

Seven-tesla susceptibility-weighted analysis of hippocampal venous structures: Application to magnetic-resonance-normal focal epilepsy.

OBJECTIVE: Vascular structures may play a significant role in epileptic pathology. Although previous attempts to characterize vasculature relative to epileptogenic zones and hippocampal sclerosis have been inconsistent, an in vivo method of analysis would assist in resolving these inconsistencies and facilitate a comparison against healthy controls in a human model. Magnetic resonance imaging is a noninvasive technique that provides excellent soft tissue contrast, and the relatively recent development of susceptibility-weighted imaging has dramatically improved the visibility of small veins. METHODS: We built and tested a Hessian-based segmentation technique, which takes advantage of the increased signal and contrast available at 7 T to detect venous structures in vivo. We investigate the ability of this technique to quantify vessels in the brain and apply it to an asymmetry analysis of vessel density in the hippocampus in patients with mesial temporal lobe epilepsy (MTLE) and neocortical epilepsy. RESULTS: Vessel density was highly symmetric in the hippocampus in controls (mean asymmetry = 0.080 ± 0.076, median = 0.05027), whereas average vessel density asymmetry was greater in neocortical (mean asymmetry = 0.23 ± 0.17, median = 0.14) and MTLE (mean asymmetry = 0.37 ± 0.46, median = 0.26) patients, with the decrease in vessel density ipsilateral to the suspected seizure onset zone. Post hoc testing with one-way analysis of variance and Tukey post hoc test indicated significant differences in the group means (P < .02) between MTLE and the control group only. SIGNIFICANCE: Asymmetry in vessel density in the hippocampus is visible in patients with MTLE, even when qualitative and quantitative measures of hippocampal asymmetry show little volumetric difference between epilepsy patients and healthy controls.

Reduced gray matter volume in the left prefrontal, occipital, and temporal regions as predictors for posttraumatic stress disorder: a voxel-based morphometric study.

The concept of acute stress disorder (ASD) was introduced as a diagnostic entity to improve the identification of traumatized people who are likely to develop posttraumatic stress disorder (PTSD). Neuroanatomical models suggest that changes in the prefrontal cortex, amygdala, and hippocampus play a role in the development of PTSD. Using voxel-based morphometry, this study aimed to investigate the predictive power of gray matter volume (GMV) alterations for developing PTSD. The GMVs of ASD patients (n = 21) were compared to those of PTSD patients (n = 17) and healthy controls (n = 18) in whole-brain and region-of-interest analyses. The GMV alterations seen in ASD patients shortly after the traumatic event (T1) were also correlated with PTSD symptom severity and symptom clusters 4 weeks later (T2). Compared with healthy controls, the ASD patients had significantly reduced GMV in the left visual cortex shortly after the traumatic event (T1) and in the left occipital and prefrontal regions 4 weeks later (T2); no significant differences in GMV were seen between the ASD and PTSD patients. Furthermore, a significant negative association was found between the GMV reduction in the left lateral temporal regions seen after the traumatic event (T1) and PTSD hyperarousal symptoms 4 weeks later (T2). Neither amygdala nor hippocampus alterations were predictive for the development of PTSD. These data suggest that gray matter deficiencies in the left hemispheric occipital and temporal regions in ASD patients may predict a liability for developing PTSD.

Acute stress alters the 'default' brain processing.

Active adaptation to acute stress is essential for coping with daily life challenges. The stress hormone cortisol, as well as large scale re-allocations of brain resources have been implicated in this adaptation. Stress-induced shifts between large-scale brain networks, including salience (SN), central executive (CEN) and default mode networks (DMN), have however been demonstrated mainly under task-conditions. It remains unclear whether such network shifts also occur in the absence of ongoing task-demands, and most critically, whether these network shifts are predictive of individual variation in the magnitude of cortisol stress-responses. In a sample of 335 healthy participants, we investigated stress-induced functional connectivity changes (delta-FC) of the SN, CEN and DMN, using resting-state fMRI data acquired before and after a socially evaluated cold-pressor test and a mental arithmetic task. To investigate which network changes are associated with acute stress, we evaluated the association between cortisol increase and delta-FC of each network. Stress-induced cortisol increase was associated with increased connectivity within the SN, but with decreased coupling of DMN at both local (within network) and global (synchronization with brain regions also outside the network) levels. These findings indicate that acute stress prompts immediate connectivity changes in large-scale resting-state networks, including the SN and DMN in the absence of explicit ongoing task-demands. Most interestingly, this brain reorganization is coupled with individuals' cortisol stress-responsiveness. These results suggest that the observed stress-induced network reorganization might function as a neural mechanism determining individual stress reactivity and, therefore, it could serve as a promising marker for future studies on stress resilience and vulnerability.

Alteration of functional brain architecture in 22q11.2 deletion syndrome - Insights into susceptibility for psychosis.

The 22q11.2 deletion is one of the most common copy number variants in humans. Carriers of the deletion have a markedly increased risk for neurodevelopmental brain disorders, including schizophrenia, autism spectrum disorders, and attention deficit hyperactivity disorder. The high risk of psychiatric disorders associated with 22q11.2 deletion syndrome offers a unique possibility to identify the functional abnormalities that precede the emergence of psychosis. Carriers of a 22q11.2 deletion show a broad range of sensory processing and cognitive abnormalities similar as in schizophrenia, such as auditory and visual sensory processing, response inhibition, working memory, social cognition, reward processing and arithmetic processing. All these processes have a significant negative impact on daily life if impaired and have been studied extensively in schizophrenia using task-based functional neuroimaging. Here, we review task-related functional brain mapping studies that have used electroencephalography or functional magnetic resonance imaging to identify functional alterations in carriers with 22q11.2 deletion syndrome within the above mentioned cognitive and sensory domains. We discuss how the identification of functional changes at the brain system level can advance the general understanding of which neurobiological alterations set the frame for the emergence of neurodevelopmental disorders in the human brain. The task-based functional neuroimaging literature shows conflicting results in many domains. Nevertheless, consistent similarities between 22q11.2 deletion syndrome and schizophrenia have been found for sensory processing, social cognition and working memory. We discuss these functional brain alterations in terms of potential biomarkers of increased risk for psychosis in the general population.

The dynamics of stress: a longitudinal MRI study of rat brain structure and connectome.

Stress is a well-established trigger for a number of neuropsychiatric disorders, as it alters both structure and function of several brain regions and its networks. Herein, we conduct a longitudinal neuroimaging study to assess how a chronic unpredictable stress protocol impacts the structure of the rat brain and its functional connectome in both high and low responders to stress. Our results reveal the changes that stress triggers in the brain, with structural atrophy affecting key regions such as the prelimbic, cingulate, insular and retrosplenial, somatosensory, motor, auditory and perirhinal/entorhinal cortices, the hippocampus, the dorsomedial striatum, nucleus accumbens, the septum, the bed nucleus of the stria terminalis, the thalamus and several brain stem nuclei. These structural changes are associated with increasing functional connectivity within a network composed by these regions. Moreover, using a clustering based on endocrine and behavioural outcomes, animals were classified as high and low responders to stress. We reveal that susceptible animals (high responders) develop local atrophy of the ventral tegmental area and an increase in functional connectivity between this area and the thalamus, further spreading to other areas that link the cognitive system with the fight-or-flight system. Through a longitudinal approach we were able to establish two distinct patterns, with functional changes occurring during the exposure to stress, but with an inflection point after the first week of stress when more prominent changes were seen. Finally, our study revealed differences in functional connectivity in a brainstem-limbic network that distinguishes resistant and susceptible responders before any exposure to stress, providing the first potential imaging-based predictive biomarkers of an individual's resilience/vulnerability to stressful conditions.

Interleukin-1 Receptor in Seizure Susceptibility after Traumatic Injury to the Pediatric Brain.

Epilepsy after pediatric traumatic brain injury (TBI) is associated with poor quality of life. This study aimed to characterize post-traumatic epilepsy in a mouse model of pediatric brain injury, and to evaluate the role of interleukin-1 (IL-1) signaling as a target for pharmacological intervention. Male mice received a controlled cortical impact or sham surgery at postnatal day 21, approximating a toddler-aged child. Mice were treated acutely with an IL-1 receptor antagonist (IL-1Ra; 100 mg/kg, s.c.) or vehicle. Spontaneous and evoked seizures were evaluated from video-EEG recordings. Behavioral assays tested for functional outcomes, postmortem analyses assessed neuropathology, and brain atrophy was detected by ex vivo magnetic resonance imaging. At 2 weeks and 3 months post-injury, TBI mice showed an elevated seizure response to the convulsant pentylenetetrazol compared with sham mice, associated with abnormal hippocampal mossy fiber sprouting. A robust increase in IL-1ß and IL-1 receptor were detected after TBI. IL-1Ra treatment reduced seizure susceptibility 2 weeks after TBI compared with vehicle, and a reduction in hippocampal astrogliosis. In a chronic study, IL-1Ra-TBI mice showed improved spatial memory at 4 months post-injury. At 5 months, most TBI mice exhibited spontaneous seizures during a 7 d video-EEG recording period. At 6 months, IL-1Ra-TBI mice had fewer evoked seizures compared with vehicle controls, coinciding with greater preservation of cortical tissue. Findings demonstrate this model's utility to delineate mechanisms underlying epileptogenesis after pediatric brain injury, and provide evidence of IL-1 signaling as a mediator of post-traumatic astrogliosis and seizure susceptibility.SIGNIFICANCE STATEMENT Epilepsy is a common cause of morbidity after traumatic brain injury in early childhood. However, a limited understanding of how epilepsy develops, particularly in the immature brain, likely contributes to the lack of efficacious treatments. In this preclinical study, we first demonstrate that a mouse model of traumatic injury to the pediatric brain reproduces many neuropathological and seizure-like hallmarks characteristic of epilepsy. Second, we demonstrate that targeting the acute inflammatory response reduces cognitive impairments, the degree of neuropathology, and seizure susceptibility, after pediatric brain injury in mice. These findings provide evidence that inflammatory cytokine signaling is a key process underlying epilepsy development after an acquired brain insult, which represents a feasible therapeutic target to improve quality of life for survivors.

Deep grey matter iron accumulation in alcohol use disorder.

PURPOSE: Evaluate brain iron accumulation in alcohol use disorder (AUD) patients compared to controls using quantitative susceptibility mapping (QSM). METHODS: QSM was performed retrospectively by using phase images from resting state functional magnetic resonance imaging (fMRI). 20 male AUD patients and 15 matched healthy controls were examined. Susceptibility values were manually traced in deep grey matter regions including caudate nucleus, combined putamen and globus pallidus, combined substantia nigra and red nucleus, dentate nucleus, and a reference white matter region in the internal capsule. Average susceptibility values from each region were compared between the patients and controls. The relationship between age and susceptibility was also explored. RESULTS: The AUD group exhibited increased susceptibility in caudate nucleus (+8.5%, p=0.034), combined putamen and globus pallidus (+10.8%, p=0.006), and dentate nucleus (+14.9%, p=0.022). Susceptibility increased with age in two of the four measured regions - combined putamen and globus pallidus (p=0.013) and combined substantia nigra and red nucleus (p=0.041). AUD did not significantly modulate the rate of susceptibility increase with age in our data. CONCLUSION: Retrospective QSM computed from standard fMRI datasets provides new opportunities for brain iron studies in psychiatry. Substantially elevated brain iron was found in AUD subjects in the basal ganglia and dentate nucleus. This was the first human AUD brain iron study and the first retrospective clinical fMRI QSM study.

Susceptible vessel sign: identification of arterial occlusion and clinical implications in acute ischaemic stroke.

AIM: To determine the accuracy of the susceptible vessel sign (SVS) in the detection of arterial occlusion and its clinical implication in acute ischaemic stroke. MATERIALS AND METHODS: Consecutive ischaemic stroke patients who underwent magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) within 24 hours of symptom onset or time last-seen-well were included. Two independent neuroradiologists reviewed the SWI for evidence of the SVS. Admission stroke severity was determined by the National Institute of Health Stroke Scale (NIHSS) scores, and poor clinical outcome was defined by a 3-months modified Rankin scale (mRS) score >2. RESULTS: The SVS was identified in 26 (12%) of 213 patients with substantial inter-reviewer agreement. The SVS had 99% specificity, 88% negative predictive value (NPV), 51% sensitivity, and 92% positive predictive value (PPV) for detection of acute arterial occlusions. In consecutive stroke patients, the presence of SVS was associated with higher admission NIHSS scores (median 9 versus 3, p<0.001), arterial occlusion (92% versus 12%, p<0.001), larger infarct volume (162±180 ml versus 25±48 ml, p=0.001), and higher rate of poor clinical outcome at 3-months follow-up (58% versus 25%, p=0.001). In the subset of patients with acute arterial occlusion (n=47), the SVS was associated with higher admission NIHSS scores (median of 10 versus 3, p=0.038) and larger infarct volumes (173±184 ml versus 76±112 ml, p=0.034). CONCLUSIONS: The SVS is a highly specific sign of occlusive arterial thrombus, and is associated with larger infarct volume and more severe presentation in a series of consecutive stroke patients, as well as in the subgroup of patients with acute arterial occlusion.

Increased cardiovascular risk without generalized arterial dilating diathesis in persons who do not have abdominal aortic aneurysm but who are first-degree relatives of abdominal aortic aneurysm patients.

There is a strong genetic predisposition towards abdominal aortic aneurysm (AAA), but it is unknown whether persons without AAA but with first-degree relatives who are AAA patients have a generalized dilating diathesis, defect arterial wall mechanics, or increased cardiovascular risk. The aim of the study was to investigate arterial diameters and wall mechanics at multiple arterial sites in these subjects and compare them with controls without a family history of AAA. This study included 118 first-degree relatives of patients with AAA and 66 controls (age: 40-80 years). The abdominal aorta, common carotid artery, common femoral artery, and popliteal artery were investigated by echo-tracking ultrasound. The relatives had no arterial dilatation, but they did tend to have smaller diameters than controls. Relatives had a higher heart rate, diastolic blood pressure, and mean arterial pressure than controls. The distensibility coefficient and the compliance coefficient were decreased in all arteries in male relatives, adjusted for age and smoking; these coefficients were normalized after adjustment for mean arterial pressure and heart rate. Female relatives had a lower compliance coefficient in the abdominal aorta, adjusted for age and smoking. After adjustment for mean arterial pressure and heart rate, the difference disappeared. No general arterial dilatation in relatives without AAA was found, supporting the hypothesis that the dilating diathesis is linked to the aneurysmal manifestation in the abdominal aorta. Although the threat of aneurysmal dilatation and rupture seems to be lacking in these subjects, heart rate, blood pressure, and arterial wall stiffness were all increased, which may indicate a higher risk of developing cardiovascular morbidity and mortality.

Preoperative MRI brain phenotypes are related to postoperative delirium in older individuals.

The underlying structural correlates of predisposition to postoperative delirium remain largely unknown. A combined analysis of preoperative brain magnetic resonance imaging (MRI) markers could improve our understanding of the pathophysiology of delirium. Therefore, we aimed to identify different MRI brain phenotypes in older patients scheduled for major elective surgery, and to assess the relation between these phenotypes and postoperative delirium. Markers of neurodegenerative and neurovascular brain changes were determined from MRI brain scans in older patients (n = 161, mean age 71, standard deviation 5 years), of whom 24 (15%) developed delirium. A hierarchical cluster analysis was performed. We found six distinct groups of patients with different MRI brain phenotypes. Logistic regression analysis showed a higher odds of developing postoperative delirium in individuals with multi-burden pathology (n = 15 (9%), odds ratio (95% confidence interval): 3.8 (1.1-13.0)). In conclusion, these results indicate that different MRI brain phenotypes are related to a different risk of developing delirium after major elective surgery. MRI brain phenotypes could assist in an improved understanding of the structural correlates of predisposition to postoperative delirium.

Imaging cerebral microbleeds in Cushing's disease evaluated by quantitative susceptibility mapping: an observational cross-sectional study.

DESIGN: Cushing's disease (CD) is a rare clinical syndrome characterized by chronic exposure to hypercortisolism due to an adrenocorticotropic hormone-secreting pituitary adenoma. The adverse effects of chronic exposure to hypercortisolism on the human brain remain unclear. The purpose of this study was to assess the prevalence of cerebral microbleeds (CMBs) in CD patients and their associations with clinical characteristics. METHODS: In this study, 48 active CD patients, 39 remitted CD patients, and 52 healthy control (HC) subjects underwent MRI. CD patients also underwent neuropsychological testing and clinical examinations. The number, locations, and volumes of CMBs were assessed on quantitative susceptibility mapping (QSM) images and with the Microbleed Anatomical Rating Scale. The correlation between CMBs and clinical characteristics was explored. RESULTS: The prevalence of CMBs among active and remitted CD patients was higher than that among HCs (16.3%, 20.5%, and 3.3%, respectively). Moreover, the age of CD patients with CMBs were much younger than HCs with CMBs. Furthermore, the increased number of CMBs in active CD patients was associated with increased cerebrospinal fluid (CSF) volumes in remitted CD patients. CONCLUSIONS: Chronic exposure to hypercortisolism may be relevant to CMBs and significantly correlated with altered brain volumes in CD.

The role of altered brain structural connectivity in resilience, vulnerability, and disease expression to schizophrenia.

BACKGROUND: Schizophrenia (SCZ) is a highly heritable disorder associated with brain connectivity changes. Although the mechanism of disease expression and vulnerability of SCZ have been reported by previous studies, the mechanism of resilience to SCZ based on the brain structural connectivity is poorly understood. The goal of the present study was to identify the structural brain connectivity related with the resilience to SCZ, which is defined here as the capacity to avoid or delay the onset of SCZ in unaffected siblings of SCZ probands. METHOD: We collected diffusion tensor imaging (DTI) data of 49 medication-naive, first-episode SCZ (FE-SCZ) patients, 56 unaffected siblings of SCZ probands (SIB-SCZ), and 90 healthy controls. Then we used graph theoretical approach to calculate the topological properties of the brain structural network, including global, subnetwork, and regional parameters. Finally, we compared the parameters between the three groups, and identified the brain structural network related to the resilience, vulnerability and disease expression to SCZ. RESULTS: With respect to resilience, only the SIB-SCZ showed significantly increased connectivity in the subnetworks of the left cuneus-precuneus and left posterior cingulate gyrus-precuneus, and in brain areas of right supramarginal gyrus and right inferior temporal gyrus. With respect to vulnerability, both the FE-SCZ and SIB-SCZ had decreased cluster coefficients and local efficiency, and decreased nodal efficiency in the right medial superior frontal gyrus and right medial orbital superior frontal gyrus compared with the healthy controls. With respect to disease expression, only the FE-SCZ group showed decreased or increased global, subnetwork, and nodal connectivity in broader brain regions compared with the healthy controls. CONCLUSION: Difference in the topological properties of brain structural connectivity not only reflect the underlying mechanism of vulnerability but also that of resilience to schizophrenia. Alteration in the brain structural connectivity associating with resilience and disease expression may contribute to the onset of SCZ.

Ultra-High Field MRI in Alzheimer's Disease: Effective Transverse Relaxation Rate and Quantitative Susceptibility Mapping of Human Brain In Vivo and Ex Vivo compared to Histology.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. So far, diagnosis of AD is only unequivocally defined through postmortem histology. Amyloid plaques are a classical hallmark of AD and amyloid load is currently quantified by Positron Emission tomography (PET) in vivo. Ultra-high field magnetic resonance imaging (UHF-MRI) can potentially provide a non-invasive biomarker for AD by allowing imaging of pathological processes at a very-high spatial resolution. The first aim of this work was to reproduce the characteristic cortical pattern previously observed in vivo in AD patients using weighted-imaging at 7T. We extended these findings using quantitative susceptibility mapping (QSM) and quantification of the effective transverse relaxation rate (R2*) at 9.4T. The second aim was to investigate the origin of the contrast patterns observed in vivo in the cortex of AD patients at 9.4T by comparing quantitative UHF-MRI (9.4T and 14.1T) of postmortem samples with histology. We observed a distinctive cortical pattern in vivo in patients compared to healthy controls (HC), and these findings were confirmed ex vivo. Specifically, we found a close link between the signal changes detected by QSM in the AD sample at 14.1T and the distribution pattern of amyloid plaques in the histological sections of the same specimen. Our findings showed that QSM and R2* maps can distinguish AD from HC at UHF by detecting cortical alterations directly related to amyloid plaques in AD patients. Furthermore, we provided a method to quantify amyloid plaque load in AD patients at UHF non-invasively.

Neural correlates of social cognition in populations at risk of psychosis: A systematic review.

Social cognition refers to the mental operations governing social interactions. Recent research has highlighted the importance of social cognition in determining functional outcome in patients with schizophrenia and in psychosis risk populations. The aim of this review is to investigate the neural correlates of social cognition in different psychosis risk populations, potentially representing different levels of risk i.e. high schizotypy (SR), familial risk (FR) and clinical high risk (CHR). PsychINFO, Web of Science and PubMed were systematically searched, and 39 papers were included in the final review. Results in FR samples were highly inconclusive. In SR samples, findings showed a tendency towards increased task related activity in frontal cortex regions. The most consistent results come from CHR samples, where findings suggest increased task related activity in frontal and cingulate cortices. Interestingly, all studies of CHR populations also report increased activity in temporal cortex and abnormal response to neutral stimuli during emotional processing tasks. These findings are discussed in relation to dopamine models of psychosis due to temporal cortex abnormality.

Relation of common carotid artery lumen diameter to general arterial dilating diathesis and abdominal aortic aneurysms: the Tromsø Study.

In a cross-sectional, population-based study in Tromsø, Norway, the authors investigated correlations between lumen diameter in the right common carotid artery (CCA) and the diameters of the femoral artery and abdominal aorta and whether CCA lumen diameter was a risk factor for abdominal aortic aneurysm (AAA). Ultrasonography was performed in 6,400 men and women aged 25-84 years during 1994-1995. An AAA was considered present if the aortic diameter at the level of renal arteries was greater than or equal to 35 mm, the infrarenal aortic diameter was greater than or equal to 5 mm larger than the diameter of the level of renal arteries, or a localized dilation of the aorta was present. CCA lumen diameter was positively correlated with abdominal aortic diameter (r = 0.3, P < 0.01) and femoral artery diameter (r = 0.2, P < 0.01). In a multivariable adjusted model, CCA lumen diameter was a significant predictor of AAA in both men and women (for the fifth quintile vs. the third, odds ratios were 1.9 (95% confidence interval: 1.2, 2.9) and 4.1 (95% confidence interval: 1.5, 10.8), respectively). Thus, CCA lumen diameter was positively correlated with femoral and abdominal aortic artery diameter and was an independent risk factor for AAA.

Females have greater susceptibility to develop ongoing pain and central sensitization in a rat model of temporomandibular joint pain.

Temporomandibular joint osteoarthritis (TMJOA) is a prevalent source of temporomandibular joint disorder (TMD). Women are more commonly diagnosed with TMD and are more likely to seek care at tertiary orofacial pain clinics. Limited knowledge regarding mechanisms underlying temporomandibular joint (TMJ) pain impairs development of improved pain management strategies. In a rat model of unilateral TMJOA, monosodium iodoacetate (MIA) produces joint pathology in a concentration-dependent manner. Unilateral MIA produces alterations in meal patterns in males and females without altering overnight time spent eating or weight across 2 weeks. Monosodium iodoacetate (80 mg/mL)-treated males develop ongoing pain within 2 weeks after MIA injection. Females develop ongoing pain at a 5-fold lower MIA concentration (16.6 mg/m). Monosodium iodoacetate (80 mg/mL)-treated males show spread of tactile hypersensitivity across the face during the first week after injection and then to the fore paws and hind paws during the second week after injection, indicating development of central sensitization. At the lower dose, female rats demonstrate a similar spread of tactile hypersensitivity, whereas male rats do not develop ongoing pain or spread of tactile hypersensitivity outside the area of the ipsilateral temporomandibular joint. These observations indicate that females have a higher susceptibility to development of ongoing pain and central sensitization compared with male rats that is not due to differences in MIA-induced joint pathology. This model of TMJOA pain can be used to explore sex differences in pain processes implicated in development of neuropathic pain, ongoing pain, and central sensitization, allowing for development of individualized strategies for prevention and treatment of TMD joint pain.

Combining quantitative susceptibility mapping to the morphometric index in differentiating between progressive supranuclear palsy and Parkinson's disease.

PURPOSE: To determine whether the susceptibility value in the deep gray matter obtained by quantitative susceptibility mapping (QSM) provides additive value to the morphometric index for differentiating progressive supranuclear palsy (PSP) from Parkinson's disease (PD). MATERIALS AND METHODS: PSP- (n = 8) and PD patients (n = 18) and 18 age-matched healthy controls who underwent QSM and 3D magnetization-prepared rapid gradient echo (MPRAGE) sequences. The mean susceptibility values (MSVs) of the deep gray matter structures on QSM- and areas of the midbrain (morphometric index, MI) on 3D MPRAGE images were measured by two neuroradiologists. Analysis of variance, the Scheffe test and receiver operating characteristic (ROC) analysis were conducted to assess differences and discriminate among PSP, PD and controls by the MSVs and the MI. Using the MSV of a structure with the best area under the curve (AUC) and the MI, we created a decision tree to differentiate between PSP and PD. RESULTS: The MSVs of the globus pallidus (GP) and substantia nigra (SN) were significantly higher in PSP than PD and the controls (p < .05). By ROC analysis (PSP vs PD), AUC was greatest (0.903) for the GP. The MI was significantly smaller in PSP than PD and the controls (p < .05); AUC (PSP vs PD) was 0.917. The decision tree using cutoff values of 244 parts per billion for MSV of the GP and 74.0 mm2 for MI served to completely differentiate between PSP and PD. CONCLUSION: The MSV in the GP on QSM images adds value to the MI for differentiating PSP from PD.

Generalized dilating diathesis in patients with popliteal arterial aneurysm.

BACKGROUND: Aim of this study was to analyse the relationship between popliteal artery aneurysm (PAA) and generalized arteriomegaly. PATIENTS AND METHODS: In this consecutive serie, thirty-three patients (1 woman, mean age 69.7 +/- 9.6 years) undergoing PAA repair between 1996 and 2000 agreed to participate in a duplex screening program to assess the diameters of the infrarenal abdominal aorta, common and external iliac, common and superficial femoral and contralateral popliteal arteries as well as common carotid and brachial arteries. RESULTS: The prevalence of arteriomegaly and aneurysmal disease, respectively, was as follows: abdominal aorta 15/33 (45.5%) and 8/33 (24.2%), common iliac artery 34/66 (51.5%) and 23/66 (34.8%), common femoral artery 55/66 (83.3%) and 7/66 (10.6%) as well as contralateral popliteal artery 7/33 (21.2%) 15/33 (45.5%). Significantly larger carotid artery diameters were found comparing PAA patients with age- and body surface adjusted healthy controls (p < 0.001). Furthermore, patients with multiple peripheral arterial aneurysms had significantly larger diameters of the brachial (p < 0.02) and external iliac (p < 0.005). CONCLUSIONS: Our findings support the hypothesis of a diathesis for a generalized arteriomegaly with a predilection for further aneurysms of the abdominal aorta, iliac arteries, femoral and contralateral popliteal arteries in patients with PAA.

Lorentzian effects in magnetic susceptibility mapping of anisotropic biological tissues.

The ultimate goal of MRI is to provide information on biological tissue microstructure and function. Quantitative Susceptibility Mapping (QSM) is one of the newer approaches for studying tissue microstructure by means of measuring phase of Gradient Recalled Echo (GRE) MRI signal. The fundamental question in the heart of this approach is: what is the relationship between the net phase/frequency of the GRE signal from an imaging voxel and the underlying tissue microstructure at the cellular and sub-cellular levels? In the presence of external magnetic field, biological media (e.g. cells, cellular components, blood) become magnetized leading to the MR signal frequency shift that is affected not only by bulk magnetic susceptibility but by the local cellular environment as well. The latter effect is often termed the Lorentzian contribution to the frequency shift. Evaluating the Lorentzian contribution - one of the most intriguing and challenging problems in this field - is the main focus of this review. While the traditional approach to this problem is based on introduction of an imaginary Lorentzian cavity, a more rigorous treatment was proposed recently based on a statistical approach and a direct solution of the Maxwell equations. This approach, termed the Generalized Lorentzian Tensor Approach (GLTA), is especially fruitful for describing anisotropic biological media. The GLTA adequately accounts for two types of anisotropy: anisotropy of magnetic susceptibility and tissue structural anisotropy (e.g., cylindrical axonal bundles in white matter). In the framework of the GLTA the frequency shift due to the local environment is described in terms of the Lorentzian tensor L̂ which can have a substantially different structure than the susceptibility tensor χ̂. While the components of χ̂ are compartmental susceptibilities "weighted" by their volume fractions, the components of L̂ are additionally weighted by specific numerical factors depending on cellular geometrical symmetry. In addition to describing the GLTA that is a phenomenological approach largely based on considering the system symmetry, we also briefly discuss a microscopic approaches to the problem that are based on modeling of the MR signal in different regimes (i.e. static dephasing vs. motion narrowing) and in different cellular environments (e.g., accounting for WM microstructure).