Metal-on-Metal Hip Replacement: MRI Signal Intensities of Different Body Tissues and Their Relations to Blood Metal Ion Levels.

BACKGROUND: Metal-on-metal total hip prostheses (MoM-THR) have been shown to produce hypersensitivity reactions and fluid collection (pseudotumor) by the hip as well as high blood metal ions levels (BMILs). OBJECTIVES: To evaluate the magnetic resonance imaging (MRI) signal-to-noise ratio (S/N) in selected body tissues around the hip of patients who underwent MoM hip replacement and to correlate to BMILs. METHODS: Sixty-one MRI hip examinations in 54 post-MoM-THR patients (18 males, 36 females, mean age 65 years) were retrospectively evaluated independently by two readers. The mean S/N ratio in a region of interest was calculated for periprosthetic pseudotumor collection (PPC), the bladder, fat, and muscle on axial T1w, FSE-T2w, and short tau inversion recovery (STIR) sequences on the same location. BMILs were retrieved from patient files. RESULTS: PPC was detected in 32 patients (52%) with an average volume of 82.48 mm3. BMIL did not correlate with the presence of PPCs but positively correlated with the PPC's volume. A trend for positive correlation was found between BMILs and S/N levels of STIR images for muscle and bladder as well as for PPC and cobalt levels. A trend for correlation was also seen between BMIL with PPC's T1 w S/N. CONCLUSIONS: Alteration of MRI S/N for different hip tissues showed a tendency for correlation with BMILs, possibly suggesting that metal deposition occurs in the PPC as well as in the surrounding tissues and bladder.

Bilateral total hip replacement: periprosthetic pseudotumor collections are more prevalent in metal-on-metal implants compared to non-metal-on-metal ones.

BACKGROUND: Metal-on-metal (MoM) hip prostheses were shown to have high failure rates including the formation of periprosthetic cystic masses called periprosthetic pseudotumor collections (PPCs). PURPOSE: To compare MRI prevalence and size of PPCs in patients after bilateral total-hip-replacement (THR) in which at least one hip was replaced by a MoM prosthesis. MATERIAL AND METHODS: All sequential MRI examinations of patients with bilateral THR in which at least one is MoM (2010-2013) were retrospectively evaluated. MRIs were analyzed separately by two readers for the presence and size of PPCs. These were compared between MoM and non-MoM implants and between patients with unilateral or bilateral-MoM prostheses. Blood metal ion levels were also compared. RESULTS: Seventy hips of 35 patients (male:female ratio, 9:26; mean age, 64 years; age range, 35-82 years) were assessed. Sixteen patients (45%) underwent bilateral MoM-THRs and 19 (55%) had one MoM and the other non-MoM, yielding 51 MoM THRs and 19 non-MoM THRs. Twenty-eight PPCs were detected in 19 patients (54%): 26 in MoM THRs (51%) and two in non-MoM THRs (10.5%, P = 0.00009). The mean PPC volume in the MoM implants (107 mm(3)) was higher than that of the non-MoM implants (18 mm(3), P = 0.49). Cobalt/chromium blood levels were 78 µg/L/25 µg/L for bilateral MoM THRs and 21 µg/L/10 µg/L for unilateral MoM implants (P = 0.1 and 0.16, respectively). CONCLUSION: PPCs are more prevalent in MoM THRs compared to non-MoM THRs. Larger PPC volumes and higher blood metal ion levels were detected in patients with bilateral MoM THRs compared to unilateral MoM THRs (P > 0.05).

Linking L2 proficiency and patterns of functional connectivity during L1 word retrieval.

Second language (L2) learners differ greatly in language proficiency, which is partially explained by variability in native language (L1) skills. The present fMRI study explored the neural underpinnings of the L1-L2 link. Twenty L2 learners completed a tip-of-the-tongue (TOT) task that required retrieving words in L1. Low-proficiency L2 learners showed greater functional connectivity for correct and TOT responses between the left inferior frontal gyrus and right-sided homologues of the temporoparietal regions that support phonological processing (e.g., supramarginal gyrus), possibly reflecting difficulty with phonological retrieval. High-proficiency L2 learners showed greater connectivity for erroneous responses (TOT in particular) between the left inferior frontal gyrus and regions of left medial temporal lobe (e.g., hippocampus), associated with implicit learning processes. The difference between low- and high-proficiency L2 learners in functional connectivity, which is evident even during L1 processing, may affect L2 learning processes and outcomes.

A new method to record and control for 2D-movement kinematics during functional magnetic resonance imaging (fMRI).

The recording of movement kinematics during functional magnetic resonance imaging (fMRI) experiments is complicated due to technical constraints of the imaging environment. Nevertheless, to study the functions of brain areas related to motor control, reliable and accurate records of movement trajectories and speed profiles are needed. We present a method designed to record and characterize the kinematic properties of drawing- and handwriting-like forearm movements during fMRI studies by recording pen stroke trajectories. The recording system consists of a translucent plastic board, a plastic pen containing fiber optics and a halogen light power source, a CCD camera, a video monitor and a PC with a video grabber card. Control experiments using a commercially available digitizer tablet have demonstrated the reliability of the data recorded during fMRI. Since the movement tracking signal is purely optical, there is no interaction with the MR (echoplanar) images. Thus, the method allows to obtain movement records with high spatial and temporal resolution which are suitable for the kinematic analysis of hand movements in fMRI studies.

In vivo occipital-frontal temperature-gradient in schizophrenia patients and its possible association with psychopathology: a magnetic resonance spectroscopy study.

BACKGROUND: Accumulating data suggest that schizophrenia patients' mental status might be modulated by their core/brain temperature. Hence, we intended to assess in vivo brain temperature (Tb) of schizophrenia patients vs. healthy subjects and to evaluate its potential association with patients' mental status. METHODS: Absolute values of Tb were measured in 9 neuroleptic-treated schizophrenia patients and 10 healthy comparison subjects using 1H magnetic resonance spectroscopy (MRS). Values were extracted by measuring the chemical shift between the peaks of water and N-acetyl-aspartate in the 1H MRS spectra. RESULTS: A substantial (about 1.1 degrees C) and significantly higher occipital-frontal temperature-gradient was found in the schizophrenia patients compared to the healthy controls (1.27 degrees C vs. 0.18 degrees C; p=0.032). Furthermore, a trend was found between the above mentioned occipital-frontal temperature-gradient in the schizophrenia patients and the severity of their psychopathology, as assessed by the total Positive and Negative Syndrome Scale (PANSS) scores (r=0.61; p=0.08). CONCLUSIONS: Our findings corroborate previous results indicating putative correlation between core/brain temperature and the mental status of schizophrenia patients, emphasizing the possible role of within patients decreased frontal temperature and a significant occipital-frontal temperature-gradient as modulators of psychopathology. In addition, the MRS technique used for brain temperature assessment seems to be a potential non-invasive method to assess in vivo absolute Tb in schizophrenia.

Magnetic resonance imaging and magnetic resonance spectroscopy in isolated sulfite oxidase deficiency.

Isolated sulfite oxidase deficiency is a rare genetic neurometabolic disease. The first symptoms of this disorder (similar to symptoms of ischemic events) may lead to misdiagnosis and to subsequent birth of affected children in these families. This study characterizes the magnetic resonance (MR) imaging and (for the first time, to our knowledge) the MR spectroscopy features of isolated sulfite oxidase deficiency to provide a means for early and correct diagnosis. Three patients with isolated sulfite oxidase deficiency are studied who manifested intractable seizures and severe hypotonia in the immediate postnatal period with an unknown diagnosis, despite extensive workup. MR imaging and proton MR spectroscopy examinations were performed early in the neonatal period in 2 infants and after 5 months in the third infant. The prominent MR features were early cystic white matter damage, accompanied by profound cerebral atrophy in the third infant. Compared with hypoxic-ischemic disorder, MR findings in isolated sulfite oxidase deficiency demonstrate a more severe condition, without subsequent recovery. The MR spectroscopy studies indicate early onset of energetic and metabolic imbalance. Urine stick findings demonstrated high sulfite levels in 2 patients, and the final diagnosis was subsequently made based on molecular, biochemical, and genetic findings. Magnetic resonance imaging and MR spectroscopy measurements may help differentiate isolated sulfite oxidase deficiency from hypoxic-ischemic condition in patients in whom this diagnosis is not clinically suspected and may lead to further genetic antenatal inquiry that might prevent the birth of other infants affected with this severe and incurable congenital disease.

Cognitive Deficits Post-Traumatic Brain Injury and Their Association with Injury Severity and Gray Matter Volumes.

Traumatic brain injury (TBI) is known to have a substantial though highly variable impact on cognitive abilities. Due to the wide range of cognitive abilities among healthy individuals, an objective assessment of TBI-related cognitive loss requires an accurate measurement of pre-morbid cognitive performance. To address this problem, we recruited 50 adults who sustained a TBI and had performed a cognitive baseline assessment in adolescence as part of the aptitude tests mandated by the Israeli Defense Forces. This group was matched with non-injured controls (n = 35). Pre- and post-injury cognitive assessments consisted of three domains-namely, verbal abstraction, mathematical reasoning, and non-verbal abstract reasoning (from the Wechsler Adult Intelligence Scale-Third Edition). The difference between post- and pre-injury scores was calculated as a measure of domain-specific cognitive decline. Voxel-based regression was used to correlate cognitive decline with modulated gray matter probability maps controlling for age, Glasgow Coma Scale, and total intracranial volume. Using objectively assessed cognitive scores, we found that abstract reasoning declined in both moderate-severe and mild TBI patients, whereas verbal abstraction declined only in the moderate-severe group. Mathematical reasoning was not affected by TBI. In the TBI patients, non-verbal abstract reasoning post-pre-injury change scores were negatively correlated with the volume of the insula. We conclude that access to pre-morbid neuropsychological data may have facilitated the discovery of the effects of mild TBI on abstract reasoning, as well as a significant correlation between TBI-related decline in this cognitive domain and the volume of the bilateral insula, both of which had not been appreciated in the past.

Haptoglobin 1-1 Genotype Modulates the Association of Glycemic Control With Hippocampal Volume in Elderly Individuals With Type 2 Diabetes.

Recent evidence suggests that glycemic control is associated with cognitive function in older patients with type 2 diabetes who are carriers of the haptoglobin (Hp) 1-1 genotype compared with noncarriers. We assessed whether poor glycemic control in Hp 1-1 carriers is more strongly associated with smaller hippocampal volume than in noncarriers. Hippocampal volume was generated from high-resolution structural T1 MRI obtained for 224 participants (28 Hp 1-1 carriers [12.5%] and 196 noncarriers [87.5%]) from the Israel Diabetes and Cognitive Decline (IDCD) study, who had a mean (SD) number of years in the Maccabi Healthcare Services (MHS) registry of 8.35 (2.63) and a mean (SD) HbA1c level of 6.66 (0.73)% [49 mmol/mol]. A stronger negative association between right hippocampal volume and HbA1c was found in patients with the Hp 1-1 genotype, with a 0.032-mL decrease in right hippocampal volume per 14% increase in HbA1c (P = 0.0007) versus a 0.009-mL decrease in Hp 1-1 noncarriers (P = 0.047), after adjusting for total intracranial volume, age, sex, follow-up years in the registry, and cardiovascular factor (interaction, P = 0.025). This indicates that 29.66% of the total variance in right hippocampal volume is explained by HbA1c levels among Hp 1-1 carriers and that 3.22% is explained by HbA1c levels among Hp 1-1 noncarriers. Our results suggest that the hippocampus of Hp 1-1 carriers may be more vulnerable to the insults of poor glycemic control.

Long-term Variability in Glycemic Control Is Associated With White Matter Hyperintensities in APOE4 Genotype Carriers With Type 2 Diabetes.

OBJECTIVE: We assessed whether the apolipoprotein ε4 (APOE4) genotype affects the relationship of variability in long-term glycemic control (measured by HbA1c SD of multiple measurements) with white matter hyperintensities (WMHs) in elderly patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: WMH volume was generated from structural T1 and fluid-attenuated inversion recovery MRI in each subject. The analysis included 124 subjects; 27 (21.8%) had one or more APOE4 alleles. RESULTS: HbA1c variability was associated with significantly higher WMH in APOE4 carriers (r = 0.47, P = 0.03), controlling for age, sex, mean HbA1c, number of follow-up years, and a composite of cardiovascular risk factors, but not in noncarriers (r = -0.04, P = 0.71; P for interaction = 0.050). CONCLUSIONS: The results suggest that the APOE4 genotype affects the relationship of long-term glycemic control with WMH load so that APOE4 carriers may be more vulnerable to the insults of poor control.

Macrophages dictate the progression and manifestation of hypertensive heart disease.

BACKGROUND: Inflammation has been implicated in the initiation, progression and manifestation of hypertensive heart disease. We sought to determine the role of monocytes/macrophages in hypertension and pressure overload induced left ventricular (LV) remodeling. METHODS AND RESULTS: We used two models of LV hypertrophy (LVH). First, to induce hypertension and LVH, we fed Sabra salt-sensitive rats with a high-salt diet. The number of macrophages increased in the hypertensive hearts, peaking at 10 weeks after a high-salt diet. Surprisingly, macrophage depletion, by IV clodronate (CL) liposomes, inhibited the development of hypertension. Moreover, macrophage depletion reduced LVH by 17% (p<0.05), and reduced cardiac fibrosis by 75%, compared with controls (p=0.001). Second, to determine the role of macrophages in the development and progression of LVH, independent of high-salt diet, we depleted macrophages in mice subjected to transverse aortic constriction and pressure overload. Significantly, macrophage depletion, for 3 weeks, attenuated LVH: a 12% decrease in diastolic and 20% in systolic wall thickness (p<0.05), and a 13% in LV mass (p=0.04), compared with controls. Additionally, macrophage depletion reduced cardiac fibrosis by 80% (p=0.006). Finally, macrophage depletion down-regulated the expression of genes associated with cardiac remodeling and fibrosis: transforming growth factor beta-1 (by 80%) collagen type III alpha-1 (by 71%) and atrial natriuretic factor (by 86%). CONCLUSIONS: Macrophages mediate the development of hypertension, LVH, adverse cardiac remodeling, and fibrosis. Macrophages, therefore, should be considered as a therapeutic target to reduce the adverse consequences of hypertensive heart disease.

Injectable collagen implant improves survival, cardiac remodeling, and function in the early period after myocarditis in rats.

AIM: Despite clear evidence of immune system involvement in the pathogenesis of myocarditis, the treatment of myocarditis remains nonspecific and supportive. We sought to test the hypothesis that injection of a collagen-based implant into the inflamed myocardium would stabilize the left ventricular (LV) wall and prevent adverse remodeling and dysfunction. METHODS AND RESULTS: Autoimmune myocarditis was induced in 42 male Lewis rats. Development of myocarditis was evaluated and confirmed by serial echocardiography and cardiac magnetic resonance scans, LV wall thickening, global and regional LV wall motion abnormalities, and in some cases pericardial effusion. Sick animals were randomized to either injectable collagen implantation or saline injection into the anterior inflamed myocardium 14 days after immunization. Significantly, injectable collagen implantation improved 31-day survival compared with controls (85.7% vs 50%; P = .03). Furthermore, although injectable collagen significantly attenuated LV systolic and diastolic dilatation and preserved LV geometry and function, control animals developed significant LV dilatation and dysfunction. These favorable effects on LV remodeling were confirmed by postmortem morphometry. Significantly, the injectable collagen implant attenuated cardiomyocyte hypertrophy and infiltration of macrophages and lymphocytes into the myocardium. CONCLUSIONS: The present study shows, for the first time, that injectable collagen biomaterial improves survival and attenuates cardiac inflammation, cardiomyocyte hypertrophy, LV remodeling, and dysfunction in the early period after myocarditis in rats. Our findings suggest a new biomaterial-based strategy to ameliorate the devastating effects of myocarditis.

Mast cell inhibition attenuates myocardial damage, adverse remodeling, and dysfunction during fulminant myocarditis in the rat.

BACKGROUND: Myocarditis is a life-threatening heart disease characterized by myocardial inflammation, necrosis, and chronic fibrosis. While mast cell inhibition has been suggested to prevent fibrosis in rat myocarditis, little is known about its effectiveness in attenuating cardiac remodeling and dysfunction in myocarditis. Thus, we sought to test the hypothesis that mast cell inhibition will attenuate the inflammatory reaction and associated left ventricular (LV) remodeling and dysfunction after fulminant autoimmune myocarditis. Methods and RESULTS: To induce experimental autoimmune myocarditis, we immunized 30 rats with porcine cardiac myosin (PCM) twice at a 7-day interval. On day 8 animals were randomized into treatment with either an intraperitoneal (IP) injection of 25mg/kg of cromolyn sodium (n = 13) or an equivalent volume (∼0.5 mL IP) of normal saline (n = 11). All animals were scanned by serial echocardiography studies before treatment (baseline echocardiogram) and after 20 days of cromolyn sodium (28 days after immunization). Furthermore, serial cardiac magnetic resonance was performed in a subgroup of 12 animals. After 20 days of treatment (28 days from first immunization), hearts were harvested for histopathological analysis. By echocardiography, cromolyn sodium prevented LV dilatation and attenuated LV dysfunction, compared with controls. Postmortem analysis of hearts showed that cromolyn sodium reduced myocardial fibrosis, as well as the number and size of cardiac mast cells in the inflamed myocardium, compared with controls. CONCLUSIONS: Our study suggests that mast cell inhibition with cromolyn sodium attenuates adverse LV remodeling and dysfunction in myocarditis. This mechanism-based therapy is clinically relevant and could improve the outcome of patients at risk for inflammatory cardiomyopathy and heart failure.

Non-invasive assessment of experimental autoimmune myocarditis in rats using a 3 T clinical MRI scanner.

AIMS: The aim of this study was to assess the use of a 3 T clinical cardiac magnetic resonance (CMR) scanner to detect injury to the heart in experimental autoimmune myocarditis (EAM). METHODS AND RESULTS: The use of 3 T CMR for the detection of cardiac injury was assessed in EAM (n = 55) and control (n = 10) male Lewis rats. Animals were evaluated with serial CMR imaging studies, using a 3 T scanner, and with 2D echocardiography before, and at 2 and 5 weeks after EAM induction. By CMR, regional wall motion abnormalities were noted in seven out of eight rats with myocarditis 5 weeks after induction. Subsequently, the rats developed significant left ventricular (LV) dilatation, wall thickening, and pericardial effusion. Average LV systolic and diastolic volumes increased from 131 ± 10 to 257 ± 20 µL (P = 0.0008), and from 309 ± 14 to 412 ± 24 µL (P < 0.0001), and ejection fraction markedly deteriorated (from 58 ± 2 to 37 ± 5%; P = 0.0003). Areas of fibrosis were located by late gadolinium enhancement (LGE) CMR at the subepicardium, mainly within the anterior, lateral, and inferior walls. The extent and location of LGE were highly correlated (r = 0.94; P < 0.0001) with areas of myocardial fibrosis by histopathology, with 85% sensitivity and 86% specificity. CONCLUSION: A clinical 3 T CMR scanner enables accurate detection, quantification, and monitoring of experimental myocarditis in rats, and could be used for translational research to study the pathophysiology of the disease and evaluate novel therapies.

Time-Resolved and Spatio-Temporal Analysis of Complex Cognitive Processes and their Role in Disorders like Developmental Dyscalculia.

The aim of this article is to report on the importance and challenges of a time-resolved and spatio-temporal analysis of fMRI data from complex cognitive processes and associated disorders using a study on developmental dyscalculia (DD). Participants underwent fMRI while judging the incorrectness of multiplication results, and the data were analyzed using a sequence of methods, each of which progressively provided more a detailed picture of the spatio-temporal aspect of this disease. Healthy subjects and subjects with DD performed alike behaviorally though they exhibited parietal disparities using traditional voxel-based group analyses. Further and more detailed differences, however, surfaced with a time-resolved examination of the neural responses during the experiment. While performing inter-group comparisons, a third group of subjects with dyslexia (DL) but with no arithmetic difficulties was included to test the specificity of the analysis and strengthen the statistical base with overall fifty-eight subjects. Surprisingly, the analysis showed a functional dissimilarity during an initial reading phase for the group of dyslexic but otherwise normal subjects, with respect to controls, even though only numerical digits and no alphabetic characters were presented. Thus our results suggest that time-resolved multi-variate analysis of complex experimental paradigms has the ability to yield powerful new clinical insights about abnormal brain function. Similarly, a detailed compilation of aberrations in the functional cascade may have much greater potential to delineate the core processing problems in mental disorders.

Alternation learning in pathological gamblers: an fMRI Study.

OBJECTIVES: We have previously reported that pathological gamblers have impaired performance on the Stroop color word naming task, go-no-go task and speed accuracy tradeoff performance, tasks used to assess executive function and interference control. The aim of the present neuroimaging study was to explore the relationship between frontal cortex function and gambling severity in pathological gamblers. MATERIALS AND METHODS: Functional MRI (fMRI) was used to estimate brain activity of ten male medication-free pathological gamblers during performance of an alternation learning task. Performance of this task has been shown to depend on the function of regions in the frontal cortex. RESULTS: The executive functions needed to perform the alternation learning task were expressed as brain activation in lateral and medial frontal as well as parietal and occipital regions. By correlating the level of local brain activation to task performance, parietal regions and lateral frontal and orbitofrontal regions were demonstrated. A higher score in SOGS was associated with intrusion on the task-specific activation in the left hemisphere, to some extant in parietal regions and even more pronouncedly in left frontal and orbitofrontal regions. CONCLUSIONS: Our preliminary data suggests that pathological gambling may be characterized by specific neuro-cognitive changes related to the frontal cortex.

Alteration learning in social anxiety disorder: an fMRI study.

The present study attempts to challenge the orbitofrontal cortex by using a learning paradigm which is specifically subserved by this cortical region. We implemented a version of alternation learning specifically designed for fMRI and assessed the cognitive performance and fMRI response in wide range of social anxiety disorder (SAD) severity (n=15). The main regions that were activated by the alternation learning task included portions of frontal and orbitofrontal cortex as well as the calcarine fissure. Correlations between brain activation and performance of the alternation learning task were found, among other regions, in the left and right orbitofrontal cortex. Highest correlations between degree of activation and the anxiety scores as assessed by the Leibovitch Social Anxiety Scale (LSAS) were obtained in the left temporal region as well as orbitofrontal cortex. This study supports the involvement of the orbitofrontal cortex in emotion and cognitive regulation in SAD.

Abnormal olfactory function demonstrated by manganese-enhanced MRI in mice with experimental neuropsychiatric lupus.

Mice with experimental neuropsychiatric lupus (NPSLE), induced by anti-ribosomal-P antibodies, developed depression-like behavior and a diminished sense of smell. Manganese-enhanced MRI (MEMRI) allows in vivo mapping of functional neuronal connections in the brain, including the olfactory tract. The aim of this study was to analyze and describe, via the MEMRI technique, the effect of the anti-ribosomal-P injection on the olfactory pathway. Twenty mice were intra-cerebra-ventricular injected to the right hemisphere: 10 with human anti-ribosomal-P antibodies and 10 with human IgG antibodies (control). Depression was addressed by forced swimming test and smell function was evaluated by smelling different concentrations of menthol. MEMRI was used to investigate the olfactory system in these mice. Passive transfer of anti-ribosomal-P to mice resulted in a depression-like behavior, accompanied with a significant deficit in olfactory function. MEMRI of these mice demonstrated significant reduction (P < 0.001) in normalized manganese enhancement ratios of olfactory structures, compared to control mice. We concluded that an impaired olfactory neuronal function in mice with experimental depression, mediated by passive transfer of human-anti-ribosomal-P, can be demonstrated by MEMRI.

Shape-selective stereo processing in human object-related visual areas.

Object related areas in the human ventral stream were previously shown to be activated, in a shape-selective manner, by luminance, motion, and texture cues. We report on the preferential activation of these areas by stereo cues defining shape. To assess the relationship of this activation to object recognition, we employed a perceptual stereo effect, which profoundly affects object recognition. The stimuli consisted of stereo-defined line drawings of objects that either protruded in front of a flat background ("front"), or were sunk into the background ("back"). Despite the similarity in the local feature structure of the two conditions, object recognition was superior in the "front" compared to the "back" configuration. We measured both recognition rates and fMRI signal from the human visual cortex while subjects viewed these stimuli. The results reveal shape selective activation from images of objects defined purely by stereoscopic cues in the human ventral stream. Furthermore, they show a significant correlation between recognition and fMRI signal in the object-related occipito-temporal cortex (lateral occipital complex).