Cortical microinfarcts in adults with Down syndrome assessed with 3T-MRI.

BACKGROUND: Cortical microinfarcts (CMI) were attributed to cerebrovascular disease and cerebral amyloid angiopathy (CAA). CAA is frequent in Down syndrome (DS) while hypertension is rare, yet no studies have assessed CMI in DS. METHODS: We included 195 adults with DS, 63 with symptomatic sporadic Alzheimer's disease (AD), and 106 controls with 3T magnetic resonance imaging. We assessed CMI prevalence in each group and CMI association with age, AD clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition in DS. RESULTS: CMI prevalence was 11.8% in DS, 4.7% in controls, and 17.5% in sporadic AD. In DS, CMI increased in prevalence with age and the AD clinical continuum, was clustered in the parietal lobes, and was associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. DISCUSSION: In DS, CMI are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic CAA phenotype. HIGHLIGHTS: This is the first study to assess cortical microinfarcts (assessed with 3T magnetic resonance imaging) in adults with Down syndrome (DS). We studied the prevalence of cortical microinfarcts in DS and its relationship with age, the Alzheimer's disease (AD) clinical continuum, vascular risk factors, vascular neuroimaging findings, amyloid/tau/neurodegeneration biomarkers, and cognition. The prevalence of cortical microinfarcts was 11.8% in DS and increased with age and along the AD clinical continuum. Cortical microinfarcts were clustered in the parietal lobes, and were associated with lacunes and cortico-subcortical infarcts, but not hemorrhagic lesions. In DS, cortical microinfarcts are posteriorly distributed and related to ischemic but not hemorrhagic findings suggesting they might be associated with a specific ischemic phenotype of cerebral amyloid angiopathy.

Exercise modifies hypothalamic connectivity and brain functional networks in women after bariatric surgery: a randomized clinical trial.

BACKGROUND: Obesity is a disease that may involve disrupted connectivity of brain networks. Bariatric surgery is an effective treatment for obesity, and the positive effects on obesity-related conditions may be enhanced by exercise. Herein, we aimed to investigate the possible synergistic effects of Roux-en-Y Gastric Bypass (RYGB) and exercise training on brain functional networks. METHODS: Thirty women eligible for bariatric surgery were randomly assigned to a Roux-en-Y gastric bypass (RYGB: n = 15, age = 41.0 ± 7.3 years) or RYGB plus Exercise Training (RYGB + ET: n = 15, age = 41.9 ± 7.2 years). Clinical, laboratory, and brain functional connectivity parameters were assessed at baseline, and 3 (POST3) and 9 months (POST9) after surgery. The 6-month, three-times-a-week, exercise intervention (resistance plus aerobic exercise) was initiated 3 months post-surgery (for RYGB + ET). RESULTS: Exercise superimposed on bariatric surgery (RYGB + ET) increased connectivity between hypothalamus and sensorial regions (seed-to-voxel analyses of hypothalamic connectivity), and decreased default mode network (DMN) and posterior salience (pSAL) network connectivity (ROI-to-ROI analyses of brain networks connectivity) when compared to RYGB alone (all p-FDR < 0.05). Increases in basal ganglia (BG) network connectivity were only observed in the exercised training group (within-group analyses). CONCLUSION: Exercise training is an important component in the management of post-bariatric patients and may improve the hypothalamic connectivity and brain functional networks that are involved in controlling food intake. TRIAL REGISTRATION: Clinicaltrial.gov: NCT02441361.

Lung ultrasound versus chest computed tomography for pregnant inpatients with COVID-19.

PURPOSE: To compare lung ultrasound (US) and computed tomography (CT) in the assessment of pregnant women with COVID-19. METHODS: Prospective study comprising 39 pregnant inpatients with COVID-19 who underwent pulmonary assessment with CT and US with a maximum span of 48 h between the exams. The thorax was divided into 12 regions and assessed in terms of the following: the presence of B-lines (>2), coalescent B-lines, consolidation on US; presence of interlobular thickening, ground glass, consolidation on CT. The two methods were scored by adding up the scores from each thoracic region. RESULTS: A significant correlation was found between the scores obtained by the two methods (rICC = 0.946; p < 0.001). They were moderately in agreement concerning the frequency of altered pulmonary regions (weighted kappa = 0.551). In US, a score over 15, coalescent B-lines, and consolidation were predictors of the need for oxygen, whereas the predictors in CT were a lung score over 16 and consolidation. The two methods, US (p < 0.001; AUC = 0.915) and CT (p < 0.001; AUC = 0.938), were fairly accurate in predicting the need for oxygen. CONCLUSION: In pregnant women, lung US and chest CT are of similar accuracy in assessing lungs affected by COVID-19 and can predict the need for oxygen.

Headache at the chronic stage of cerebral venous thrombosis.

BACKGROUND: Headache is the most frequent symptom of cerebral venous thrombosis (CVT) but there is limited information about the frequency and phenotype of headache, weeks to months after cerebral venous thrombosis (post-cerebral venous thrombosis headache, PCH). OBJECTIVE: To assess the frequency, characteristics and predictors of PCH. METHODS: In this cross-sectional study, the frequency and characteristics of PCH were assessed in cerebral venous thrombosis survivors. Patients were interviewed between six months and five years after the cerebral venous thrombosis diagnosis. Clinical and imaging characteristics at the time of cerebral venous thrombosis diagnosis, as well as history of headache prior to cerebral venous thrombosis were compared in subjects with (GroupPCH) and without PCH (Groupcontrol). RESULTS: Subjects (n = 100; 82% women) were assessed, on average, at 1.1 ± 1.6 years of follow-up. PCH was present in 59% of the patients, phenotypes of tension-type-like headache were present in 31/59 (52.6%) and of migraine-like headache in 16/59 (27.1%). History of primary headache prior to cerebral venous thrombosis was significantly more common (OR: 6.4; 95% CI: 1.7-36.3) in GroupPCH (33.9%) than in Groupcontrol (7.3%). CONCLUSION: PCH was present in more than half of the patients. History of prior headache may be a risk factor for PCH. Prospective studies are required to confirm these findings and determine mechanisms, as well as interventions for prevention and treatment of PCH.

Pre-treatment MRI tumor features and post-treatment mammographic findings: may they contribute to refining the prediction of pathologic complete response in post-neoadjuvant breast cancer patients with radiologic complete response on MRI?

PURPOSE: Radiologic complete response (rCR) in breast cancer patients after neoadjuvant chemotherapy (NAC) does not necessarily correlate with pathologic complete response (pCR), a marker traditionally associated with better outcomes. We sought to verify if data extracted from two important steps of the imaging workup (tumor features at pre-treatment MRI and post-treatment mammographic findings) might assist in refining the prediction of pCR in post-NAC patients showing rCR. METHODS: A total of 115 post-NAC women with rCR on MRI (2010-2016) were retrospectively assessed. Pre-treatment MRI (lesion morphology, size, and distribution) and post-treatment mammographic findings (calcification, asymmetry, mass, architectural distortion) were assessed, as well as clinical and molecular variables. Bivariate and multivariate analyses evaluated correlation between such variables and pCR. Post-NAC mammographic findings and their correlation with ductal in situ carcinoma (DCIS) were evaluated using Pearson's correlation. RESULTS: Tumor distribution at pre-treatment MRI was the only significant predictive imaging feature on multivariate analysis, with multicentric lesions having lower odds of pCR (p = 0.035). There was no significant association between tumor size and morphology with pCR. Mammographic residual calcifications were associated with DCIS (p = 0.009). The receptor subtype remained as a significant predictor, with HR-HER2 + and triple-negative status demonstrating higher odds of pCR on multivariate analyses. CONCLUSIONS: Multicentric lesions on pre-NAC MRI were associated with a lower chance of pCR in post-NAC rCR patients. The receptor subtype remained a reliable predictor of pCR. Residual mammographic calcifications correlated with higher odds of malignancy, making the correlation between mammography and MRI essential for surgical planning. Key Points • The presence of a multicentric lesion on pre-NAC MRI, even though the patient reaches a radiologic complete response on MRI, is associated with a lower chance of pCR. • Molecular status of the tumor remained the only significant predictor of pathologic complete response in such patients in the present study. • Post-neoadjuvant residual calcifications found on mammography were related to higher odds of residual malignancy, making the correlation between mammography and MRI essential for surgical planning.

Imaging Aspects of the Hippocampus.

The hippocampus is one of the most sophisticated structures in the brain, owing to its complex anatomy, intriguing functions, relationship with other structures, and relevant associated symptoms. Despite being a structure analyzed for centuries, its anatomy and physiology in the human body are still being extensively studied, as well as associated pathologic conditions and potential biomarkers. It can be affected by a broad group of diseases that can be classified as congenital, degenerative, infectious or inflammatory, neoplastic, vascular, or toxic-metabolic disease. The authors present the anatomy and close structures, function, and development of the hippocampus, as well as an original algorithm for imaging diagnosis. The algorithm includes pathologic conditions that typically affect the hippocampus and groups them into nodular (space occupying) and nonnodular pathologic conditions, serving as a guide to narrow the differential diagnosis. MRI is the imaging modality of choice for evaluation of the hippocampus, and CT and nuclear medicine also improve the analysis. The MRI differential diagnosis depends on anatomic recognition and careful characterization of associated imaging findings such as volumetric changes, diffusion restriction, cystic appearance, hyperintensity at T1-weighted imaging, enhancement, or calcification, which play a central role in diagnosis along with clinical findings. Some pathologic conditions arising from surrounding structures such as the amygdala are also important to recognize. Pathologic conditions of the hippocampus can be a challenge to diagnose because they usually manifest as similar clinical syndromes, so the imaging findings play a potential role in guiding the final diagnosis. Online supplemental material is available for this article. ©RSNA, 2022.

DTI-derived parameters differ between moderate and severe traumatic brain injury and its association with psychiatric scores.

BACKGROUND AND AIM: Diffusion tensor imaging (DTI) parameters in the corpus callosum have been suggested to be a biomarker for prognostic outcomes in individuals with diffuse axonal injury (DAI). However, differences between the DTI parameters on moderate and severe trauma in DAI over time are still unclear. A secondary goal was to study the association between the changes in the DTI parameters, anxiety, and depressive scores in DAI over time. METHODS: Twenty subjects were recruited from a neurological outpatient clinic and evaluated at 2, 6, and 12 months after the brain injury and compared to matched age and sex healthy controls regarding the DTI parameters in the corpus callosum. State-Trace Anxiety Inventory and Beck Depression Inventory were used to assess psychiatric outcomes in the TBI group over time. RESULTS: Differences were observed in the fractional anisotropy and mean diffusivity of the genu, body, and splenium of the corpus callosum between DAI and controls (p < 0.02). Differences in both parameters in the genu of the corpus callosum were also detected between patients with moderate and severe DAI (p < 0.05). There was an increase in the mean diffusivity values and the fractional anisotropy decrease in the DAI group over time (p < 0.02). There was no significant correlation between changes in the fractional anisotropy and mean diffusivity across the study and psychiatric outcomes in DAI. CONCLUSION: DTI parameters, specifically the mean diffusivity in the corpus callosum, may provide reliable characterization and quantification of differences determined by the brain injury severity. No correlation was observed with DAI parameters and the psychiatric outcome scores.

Hippocampal subregional volume changes in elders classified using positron emission tomography-based Alzheimer's biomarkers of ß-amyloid deposition and neurodegeneration.

Changes in hippocampal subfield volumes (HSV) along the Alzheimer's disease (AD) continuum have been scarcely investigated to date in elderly subjects classified based on the presence of ß-amyloid aggregation and signs of neurodegeneration. We classified patients (either sex) with mild dementia compatible with AD (n = 35) or amnestic mild cognitive impairment (n = 39), and cognitively unimpaired subjects (either sex; n = 26) using [11 C]PIB-PET to assess ß-amyloid aggregation (A+) and [18 F]FDG-PET to account for neurodegeneration ((N)+). Magnetic resonance imaging-based automated methods were used for HSV and white matter hyperintensity (WMH) measurements. Significant HSV reductions were found in A+(N)+ subjects in the presubiculum/subiculum complex and molecular layer, related to worse memory performance. In both the A+(N)+ and A+(N)- categories, subicular volumes were inversely correlated with the degree of Aß deposition. The A-(N)+ subgroup showed reduced HSV relative to the A-(N)- subgroup also in the subiculum/presubiculum. Combining all (N)- subjects, HSV were lower in subjects presenting significant cognitive decline irrespective of A+/A- classification (controlling for WMH load); these between-group differences were detected again in the presubiculum, but also involved the CA4 and granular layer. These findings demonstrate that differential HSV reductions are detectable both in (N)+ and (N)- categories along the AD continuum, and are directly related to the severity of cognitive deficits. HSV reductions are larger both in A+(N)+ and A+(N)- subjects in direct proportion to the degree of Aß deposition. The meaningful HSV reductions detected in the A-(N)+ subgroup highlights the strength of biomarker-based classifications outside of the classical AD continuum.

Prostatic Artery Embolization: Indications, Preparation, Techniques, Imaging Evaluation, Reporting, and Complications.

Benign prostatic hyperplasia (BPH) is a noncancerous growth of the transitional zone of the prostate, which surrounds the prostatic urethra. Consequently, it can cause lower urinary tract symptoms (LUTS) and bladder outlet obstruction symptoms that may substantially reduce a patient's quality of life. Several treatments are available for BPH, including medications such as α-blockers and 5α-reductase inhibitors and surgical options including transurethral resection of the prostate and prostatectomy. Recently, prostatic artery embolization (PAE) has emerged as a minimally invasive treatment option for selected men with BPH and moderate to severe LUTS. Adequate pre- and postprocedural evaluations with clinical examinations and questionnaires, laboratory tests, and urodynamic and imaging examinations (particularly US, MRI, and CT) are of key importance to achieve successful treatment. Considering that the use of PAE has been increasing in tertiary hospital facilities, radiologists and interventional radiologists should be aware of the main technical concepts of PAE and the key features to address in imaging reports in pre- and postprocedural settings. An invited commentary by Lopera is available online. Online supplemental material is available for this article. ©RSNA, 2021.

Understanding brain resilience in superagers: a systematic review.

PURPOSE: Superagers are older adults presenting excellent memory performance that may reflect resilience to the conventional pathways of aging. Our contribution aims to shape the evidence body of the known distinctive biomarkers of superagers and their connections with the Brain and Cognitive Reserve and Brain Maintenance concepts. METHODS: We performed a systematic literature search in PubMed and ScienceDirect with no limit on publication date for studies that evaluated potential biomarkers in superagers classified by validated neuropsychological tests. Methodological quality was assessed using the QUADAS-2 tool. RESULTS: Twenty-one studies were included, the majority in neuroimaging, followed by histological, genetic, cognition, and a single one on blood plasma analysis. Superagers exhibited specific regions of cortical preservation, rather than global cortical maintenance, standing out the anterior cingulate and hippocampus regions. Both superagers and controls showed similar levels of amyloid deposition. Moreover, the functional oscillation patterns in superagers resembled those described in young adults. Most of the quality assessment for the included studies showed medium risks of bias. CONCLUSION: This systematic review supports selective cortical preservation in superagers, comprehending regions of the default mode, and salience networks, overlapped by stronger functional connectivity. In this context, the anterior cingulate cortex is highlighted as an imaging and histologic signature of these subjects. Besides, the biomarkers included pointed out that the Brain and Cognitive Reserve and Brain Maintenance concepts are independent and complementary in the superagers' setting.

ACC Glu/GABA ratio is decreased in euthymic bipolar disorder I patients: possible in vivo neurometabolite explanation for mood stabilization.

Bipolar disorder (BD) is characterized by unstable mood states ranging from mania to depression. Although there is some evidence that mood instability may result from an imbalance between excitatory glutamatergic and inhibitory GABA-ergic neurotransmission, few proton magnetic resonance spectroscopy (1H-MRS) studies have measured these two neurometabolites simultaneously in BD. The enzyme glutamic acid decarboxylase (GAD1) catalyzes the decarboxylation of glutamate (Glu) to GABA, and its single nucleotide polymorphisms (SNPs) might influence Glu/GABA ratio. Thus, we investigated Glu/GABA ratio in the dorsal anterior cingulate cortex (dACC) of euthymic BD type I patients and healthy controls (HC), and assessed the influence of both mood stabilizers and GAD1 SNPs on this ratio. Eighty-eight subjects (50 euthymic BD type I patients and 38 HC) underwent 3T 1H-MRS in the dACC (2 × 2 × 4.5 cm3) using a two-dimensional JPRESS sequence and all subjects were genotyped for 4 SNPs in the GAD1 gene. BD patients had lower dACC Glu/GABA ratio compared to HC, where this was influenced by anticonvulsant and antipsychotic medications, but not lithium. The presence of GAD1 rs1978340 allele A was associated with higher Glu/GABA ratio in BD, while patients without this allele taking mood stabilizers had a lower Glu/GABA ratio. The lowering of dACC Glu/GABA could be one explanation for the mood stabilizing action of anticonvulsants and antipsychotics in BD type I euthymia. Therefore, this putative role of Glu/GABA ratio and the influence of GAD1 genotype interacting with mood stabilization medication should be confirmed by further studies involving larger samples and other mood states.ClincalTrials.gov registration: NCT01237158.

Dynamic changes in white matter following traumatic brain injury and how diffuse axonal injury relates to cognitive domain.

Objective: The goal is to evaluate longitudinally with diffusion tensor imaging (DTI) the integrity of cerebral white matter in patients with moderate and severe DAI and to correlate the DTI findings with cognitive deficits.Methods: Patients with DAI (n = 20) were scanned at three timepoints (2, 6 and 12 months) after trauma. A healthy control group (n = 20) was evaluated once with the same high-field MRI scanner. The corpus callosum (CC) and the bilateral superior longitudinal fascicles (SLFs) were assessed by deterministic tractography with ExploreDTI. A neuropschychological evaluation was also performed.Results: The CC and both SLFs demonstrated various microstructural abnormalities in between-groups comparisons. All DTI parameters demonstrated changes across time in the body of the CC, while FA (fractional anisotropy) increases were seen on both SLFs. In the splenium of the CC, progressive changes in the mean diffusivity (MD) and axial diffusivity (AD) were also observed. There was an improvement in attention and memory along time. Remarkably, DTI parameters demonstrated several correlations with the cognitive domains.Conclusions: Our findings suggest that microstructural changes in the white matter are dynamic and may be detectable by DTI throughout the first year after trauma. Likewise, patients also demonstrated improvement in some cognitive skills.

Gray matter networks and cognitive impairment in multiple sclerosis.

BACKGROUND: Coordinated patterns of gray matter morphology can be represented as networks, and network disruptions may explain cognitive dysfunction related to multiple sclerosis (MS). OBJECTIVE: To investigate whether single-subject gray matter network properties are related to impaired cognition in MS. METHODS: We studied 148 MS patients (99 female) and 33 healthy controls (HC, 21 female). Seven network parameters were computed and compared within MS between cognitively normal and impaired subjects, and associated with performance on neuropsychological tests in six cognitive domains with regression models. Analyses were controlled for age, gender, whole-brain gray matter volumes, and education level. RESULTS: Compared to MS subjects with normal cognition, MS subjects with cognitive impairment showed a more random network organization as indicated by lower lambda values (all p < 0.05). Worse average cognition and executive function were associated with lower lambda values. Impaired information processing speed, working memory, and attention were associated with lower clustering values. CONCLUSION: Our findings indicate that MS subjects with a more randomly organized gray matter network show worse cognitive functioning, suggesting that single-subject gray matter graphs may capture neurological dysfunction due to MS.

Adult Leukodystrophies: A Step-by-Step Diagnostic Approach.

Leukodystrophies usually affect children, but in the last several decades, many instances of adult leukodystrophies have been reported in the medical literature. Because the clinical manifestation of these diseases can be nonspecific, MRI can help with establishing a diagnosis. A step-by-step approach to assist in the diagnosis of adult leukodystrophies is proposed in this article. The first step is to identify symmetric white matter involvement, which is more commonly observed in these patients. The next step is to fit the symmetric white matter involvement into one of the proposed patterns. However, a patient may present with more than one pattern of white matter involvement. Thus, the third step is to evaluate for five distinct characteristics-including enhancement, lesions with signal intensity similar to that of cerebrospinal fluid, susceptibility-weighted MRI signal intensity abnormalities, abnormal peaks at MR spectroscopy, and spinal cord involvement-to further narrow the differential diagnosis. ©RSNA, 2019.

Imaging Patterns of Toxic and Metabolic Brain Disorders.

Toxic and metabolic brain disorders are relatively uncommon diseases that affect the central nervous system, but they are important to recognize as they can lead to catastrophic outcomes if not rapidly and properly managed. Imaging plays a key role in determining the most probable diagnosis, pointing to the next steps of investigation, and providing prognostic information. The majority of cases demonstrate bilateral and symmetric involvement of structures at imaging, affecting the deep gray nuclei, cortical gray matter, and/or periventricular white matter, and some cases show specific imaging manifestations. When an appropriate clinical situation suggests exogenous or endogenous toxic effects, the associated imaging pattern usually indicates a restricted group of diagnostic possibilities. Nonetheless, toxic and metabolic brain disorders in the literature are usually approached in the literature by starting with common causal agents and then reaching imaging abnormalities, frequently mixing many different possible manifestations. Conversely, this article proposes a systematic approach to address this group of diseases based on the most important imaging patterns encountered in clinical practice. Each pattern is suggestive of a most likely differential diagnosis, which more closely resembles real-world scenarios faced by radiologists. Basic pathophysiologic concepts regarding cerebral edemas and their relation to imaging are introduced-an important topic for overall understanding. The most important imaging patterns are presented, and the main differential diagnosis for each pattern is discussed. Online supplemental material is available for this article. ©RSNA, 2019.

Is possible to rule out clinically significant prostate cancer using PI-RADS v2 for the assessment of prostate MRI?

OBJECTIVES: To evaluate the diagnostic performance and interobserver agreement of PI-RADS v2. MATERIALS AND METHODS: In this Institutional Review Board approved single-center retrospective study, 98 patients with clinically suspected PCa who underwent 3-T multiparametric MRI followed by MRI/TRUS fusion-guided prostate biopsy were included from June 2013 to February 2015. Two radiologists (R1 and R2) with 8 and 1 years of experience in abdominal radiology reviewed the MRI scans and assigned PI-RADS v2 scores in all prostate zones. PI-RADS v2 were compared to MRI/TRUS fusion-guided biopsy results, which were classified as negative, PCa, and significant PCa (sPCa). RESULTS: Sensitivity, specificity, NPV, PPV and accuracy for PCa was 85.7% (same for all metrics) for R1 and 81.6%, 79.6%, 81.2%, 80.0% and 80.6% for R2. For detecting sPCa, the corresponding values were 95.3%, 85.4%, 95.9%, 83.7% and 89.8% for R1 and 93.0%, 81.8%, 93.7%, 86.7% and 86.7% for R2. There was substantial interobserver agreement in assigning PI-RADS v2 score as negative (1, 2, 3) or positive (4, 5) (Kappa=0.78). On multivariate analysis, PI-RADS v2 (p <0.001) was the only independent predictor of sPCa compared with age, abnormal DRE, prostate volume, PSA and PSA density. CONCLUSIONS: Our study population demonstrated that PI-RADS v2 had high diagnostic accuracy, substantial interobserver agreement, and it was the only independent predictor of sPCa.

Longitudinal changes in brain volumetry and cognitive functions after moderate and severe diffuse axonal injury.

BACKGROUND AND OBJECTIVE: Diffuse axonal injury (DAI) induces a long-term process of brain atrophy and cognitive deficits. The goal of this study was to determine whether there are correlations between brain volume loss, microhaemorrhage load (MHL) and neuropsychological performance during the first year after DAI. METHODS: Twenty-four patients with moderate or severe DAI were evaluated at 2, 6 and 12 months post-injury. MHL was evaluated at 3 months, and brain volumetry was evaluated at 3, 6 and 12 months. The trail making test (TMT) was used to evaluate executive function (EF), and the Hopkins verbal learning test (HVLT) was used to evaluate episodic verbal memory (EVM) at 6 and 12 months. RESULTS: There were significant white matter volume (WMV), subcortical grey matter volume and total brain volume (TBV) reductions during the study period (p < 0.05). MHL was correlated only with WMV reduction. EF and EVM were not correlated with MHL but were, in part, correlated with WMV and TBV reductions. CONCLUSIONS: Our findings suggest that MHL may be a predictor of WMV reduction but cannot predict EF or EVM in DAI. Brain atrophy progresses over time, but patients showed better EF and EVM in some of the tests, which could be due to neuroplasticity.

Increased Brain Lactate During Depressive Episodes and Reversal Effects by Lithium Monotherapy in Drug-Naive Bipolar Disorder: A 3-T 1H-MRS Study.

OBJECTIVE: Mitochondrial dysfunction and energy metabolism impairment are key components in the pathophysiology of bipolar disorder (BD) and may involve a shift from aerobic to anaerobic metabolism. Measurement of brain lactate in vivo using proton magnetic resonance spectroscopy (H-MRS) represents an important tool to evaluate mitochondrial and metabolic dysfunction during mood episodes, as well as to monitor treatment response. To date, very few studies have quantified brain lactate in BD. In addition, no study has longitudinally evaluated lactate using H-MRS during depressive episodes or its association with mood stabilizer therapy. This study aimed to evaluate cingulate cortex (CC) lactate using 3-T H-MRS during acute depressive episodes in BD and the possible effects induced by lithium monotherapy. METHODS: Twenty medication-free outpatients with short length of BD (80% drug-naive) in a current major depressive episode were matched with control subjects. Patients were treated for 6 weeks with lithium monotherapy at therapeutic doses in an open-label trial (blood level, 0.48 ± 0.19 mmol/L). Cingulate cortex lactate was measured before (week 0) and after lithium therapy (week 6) using H-MRS. Antidepressant efficacy was assessed with the 21-item Hamilton Depression Rating Scale as the primary outcome. RESULTS: Subjects with BD depression showed a significantly higher CC lactate in comparison to control subjects. Furthermore, a significant decrease in CC lactate was observed after 6 weeks of lithium treatment compared with baseline (P = 0.002). CC Lactate levels was associated with family history of mood disorders and plasma lithium levels. CONCLUSIONS: This is the first report of increased CC lactate in patients with bipolar depression and lower levels after lithium monotherapy for 6 weeks. These findings indicate a shift to anaerobic metabolism and a role for lactate as a state marker during mood episodes. Energy and redox dysfunction may represent key targets for lithium's therapeutic actions.

Substantia nigra fractional anisotropy is not a diagnostic biomarker of Parkinson's disease: A diagnostic performance study and meta-analysis.

OBJECTIVES: Our goal was to estimate the diagnostic accuracy of substantia nigra fractional anisotropy (SN-FA) for Parkinson's disease (PD) diagnosis in a sample similar to the clinical setting, including patients with essential tremor (ET) and healthy controls (HC). We also performed a systematic review and meta-analysis to estimate mean change in SN-FA induced by PD and its diagnostic accuracy. METHODS: Our sample consisted of 135 subjects: 72 PD, 21 ET and 42 HC. To address inter-scanner variability, two 3.0-T MRI scans were performed. MRI results of this sample were pooled into a meta-analysis that included 1,432 subjects (806 PD and 626 HC). A bivariate model was used to evaluate diagnostic accuracy measures. RESULTS: In our sample, we did not observe a significant effect of disease on SN-FA and it was uninformative for diagnosis. The results of the meta-analysis estimated a 0.03 decrease in mean SN-FA in PD relative to HC (CI: 0.01-0.05). However, the discriminatory capability of SN-FA to diagnose PD was low: pooled sensitivity and specificity were 72 % (CI: 68-75) and 63 % (CI: 58-70), respectively. There was high heterogeneity between studies (I2 = 91.9 %). CONCLUSIONS: SN-FA cannot be used as an isolated measure to diagnose PD. KEY POINTS: • SN-FA appears insufficiently sensitive and specific to diagnose PD. • Radiologists must be careful when translating mean group results to clinical practice. • Imaging protocol and analysis standardization is necessary for developing reproducible quantitative biomarkers.

Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study.

OBJECTIVE: Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls. METHODS: Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm(3)) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program. RESULTS: Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed. CONCLUSION: This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis.