Diagnostic and Predictive Applications of Functional Near-Infrared Spectroscopy for Major Depressive Disorder: A Systematic Review.

INTRODUCTION: Major depressive disorder (MDD) is a global psychiatric disorder with no established biomarker. There is growing evidence that functional near-infrared spectroscopy (fNIRS) has the ability to aid in the diagnosis and prediction of the treatment response of MDD. The aim of this review was to systematically review, and gather the evidence from existing studies that used fNIRS signals in the diagnosis of MDD, correlations with depression symptomatology, and the monitoring of treatment response. METHODS: PubMed, EMBASE, ScienceDirect, and Cochrane Library databases were searched for published English articles from 1980 to June 2019 that focused on the application of fNIRS for (i) differentiating depressed versus nondepressed individuals, (ii) correlating with depression symptomatology, and in turn (iii) monitoring treatment responses in depression. Studies were included if they utilized fNIRS to evaluate cerebral hemodynamic variations in patients with MDD of any age group. The quality of the evidence was assessed using the Newcastle-Ottawa quality assessment scale. RESULTS: A total of 64 studies were included in this review, with 12 studies being longitudinal, while the rest were cross-sectional. More than two-thirds of the studies (n = 49) had acceptable quality. fNIRS consistently demonstrated attenuated cerebral hemodynamic changes in depressed compared to healthy individuals. fNIRS signals have also shown promise in correlating with individual symptoms of depression and monitoring various treatment responses. CONCLUSIONS: This review provides comprehensive updated evidence of the diagnostic and predictive applications of fNIRS in patients with MDD. Future studies involving larger sample sizes, standardized methodology, examination of more brain regions in an integrative approach, and longitudinal follow-ups are needed.

Stenosis detection and quantification on cardiac CTCA using panoramic MIP of coronary arteries.

In this work, we proposed to demonstrate the entire 3D coronary tree using panoramic maximum intensity projection (MIP) of coronary arteries, and to detect and quantify coronary stenosis from computed tomography coronary angiography (CTCA). The performance of the proposed method was assessed in comparison with invasive coronary angiography (ICA) as reference standard. Six anonymized CTCA datasets were tested. MIP method achieved a sensitivity of 82% and a specificity of 95% for the stenosis detection with a good reproducibility (i.e. Cohen's kappa coefficient of 0.74 for the intra-rater agreement, and 0.45 for the inter-raters agreement). In stenosis quantification, three image options are provided. The original density images resulted in an accuracy of 0.85. The edge map images resulted in an accuracy of 0.79. The image combination had a better accuracy of 0.89 than any single image option. In conclusion, the panoramic MIP provided fast and accurate way for the stenosis detection and quantification. It may be helpful to assist the radiologist in identifying the location of the greatest narrowing in clinical practice.

Testosterone effect on brain metabolism in elderly patients with Alzheimer's disease: comparing two cases at different disease stages.

OBJECTIVE: To describe the effect of testosterone replacement therapy (TRT) on the brain activity of two demented, hypogonadal male patients with early and late-stage Alzheimer's disease (AD), respectively. METHODS: We describe the clinical and positron emission tomography (PET) findings for two individuals, one with early stage and the other with late-stage Alzheimer's disease, before and after treatment with a topical testosterone gel. Both patients were hypogonadal at baseline. We assessed cerebral glucose metabolism (CGM) via (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). We investigated whether there are testosterone-susceptible areas within cerebral structures in patients with Alzheimer's disease. RESULTS: Under testosterone replacement therapy, changes in cerebral glucose metabolism were observed in both patients. Improvement in glucose uptake was observed most consistently in the parietal lobe and brainstem; decreased glucose metabolism was observed in the temporal lobe, the limbic system and the insula for these two subjects. DISCUSSION: These case reports demonstrate the potential for PET scanning to detect changes in cerebral glucose metabolism in hypogonadal men with Alzheimer's disease who are treated with testosterone. Further study will be needed to investigate the consistency and significance of these changes in terms of magnitude and brain region, and the correlation with functional changes.

Left ventricular wall stress compendium.

Left ventricular (LV) wall stress has intrigued scientists and cardiologists since the time of Lame and Laplace in 1800s. The left ventricle is an intriguing organ structure, whose intrinsic design enables it to fill and contract. The development of wall stress is intriguing to cardiologists and biomedical engineers. The role of left ventricle wall stress in cardiac perfusion and pumping as well as in cardiac pathophysiology is a relatively unexplored phenomenon. But even for us to assess this role, we first need accurate determination of in vivo wall stress. However, at this point, 150 years after Lame estimated left ventricle wall stress using the elasticity theory, we are still in the exploratory stage of (i) developing left ventricle models that properly represent left ventricle anatomy and physiology and (ii) obtaining data on left ventricle dynamics. In this paper, we are responding to the need for a comprehensive survey of left ventricle wall stress models, their mechanics, stress computation and results. We have provided herein a compendium of major type of wall stress models: thin-wall models based on the Laplace law, thick-wall shell models, elasticity theory model, thick-wall large deformation models and finite element models. We have compared the mean stress values of these models as well as the variation of stress across the wall. All of the thin-wall and thick-wall shell models are based on idealised ellipsoidal and spherical geometries. However, the elasticity model's shape can vary through the cycle, to simulate the more ellipsoidal shape of the left ventricle in the systolic phase. The finite element models have more representative geometries, but are generally based on animal data, which limits their medical relevance. This paper can enable readers to obtain a comprehensive perspective of left ventricle wall stress models, of how to employ them to determine wall stresses, and be cognizant of the assumptions involved in the use of specific models.

Impact of surgical ventricular restoration on ventricular shape, wall stress, and function in heart failure patients.

Surgical ventricular restoration (SVR) was designed to treat patients with aneurysms or large akinetic walls and dilated ventricles. Yet, crucial aspects essential to the efficacy of this procedure like optimal shape and size of the left ventricle (LV) are still debatable. The objective of this study is to quantify the efficacy of SVR based on LV regional shape in terms of curvedness, wall stress, and ventricular systolic function. A total of 40 patients underwent magnetic resonance imaging (MRI) before and after SVR. Both short-axis and long-axis MRI were used to reconstruct end-diastolic and end-systolic three-dimensional LV geometry. The regional shape in terms of surface curvedness, wall thickness, and wall stress indexes were determined for the entire LV. The infarct, border, and remote zones were defined in terms of end-diastolic wall thickness. The LV global systolic function in terms of global ejection fraction, the ratio between stroke work (SW) and end-diastolic volume (SW/EDV), the maximal rate of change of pressure-normalized stress (dσ*/dt(max)), and the regional function in terms of surface area change were examined. The LV end-diastolic and end-systolic volumes were significantly reduced, and global systolic function was improved in ejection fraction, SW/EDV, and dσ*/dt(max). In addition, the end-diastolic and end-systolic stresses in all zones were reduced. Although there was a slight increase in regional curvedness and surface area change in each zone, the change was not significant. Also, while SVR reduced LV wall stress with increased global LV systolic function, regional LV shape and function did not significantly improve.

Revisiting the effect of referral bias on the clinical spectrum of infective endocarditis in adults.

Referral bias occurs because of the clustering of patients at tertiary care centers. This may result in the distortion of observed clinical manifestations of rare diseases. This analysis evaluates the effect of referral bias on the epidemiology of infective endocarditis (IE) in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS). This is a prospective multicenter cohort study comparing transferred and non-transferred patients with IE. Factors independently associated with transfer status were evaluated using multivariable logistic regression. A total of 2,760 patients were included in the analysis, of which 1,164 (42.2%) were transferred from other medical centers. Transferred patients more often underwent surgery for IE (odds ratio [OR] = 2.5; 95% confidence interval [CI] 1.9-3.2). They were also more likely to have complications such as stroke (OR = 1.5; 95% CI 1.3-1.9), heart failure (OR = 1.4; 95% CI 1.1-1.6), and new valvular regurgitation (OR = 1.3; 95% CI 1.1-1.6). The in-hospital mortality rates were similar in both groups. Patients with IE who require surgery and suffer complications are referred to tertiary hospitals more frequently than patients with an uncomplicated course. Hospital transfer has no obvious effect on the in-hospital mortality. Referral bias should be taken into consideration when describing the clinical spectrum of IE.

Anabolic steroid-induced hypogonadism--towards a unified hypothesis of anabolic steroid action.

Anabolic steroid-induced hypogonadism (ASIH) is the functional incompetence of the testes with subnormal or impaired production of testosterone and/or spermatozoa due to administration of androgens or anabolic steroids. Anabolic-androgenic steroid (AAS), both prescription and nonprescription, use is a cause of ASIH. Current AAS use includes prescribing for wasting associated conditions. Nonprescription AAS use is also believed to lead to AAS dependency or addiction. Together these two uses account for more than four million males taking AAS in one form or another for a limited duration. While both of these uses deal with the effects of AAS administration they do not account for the period after AAS cessation. The signs and symptoms of ASIH directly impact the observation of an increase in muscle mass and muscle strength from AAS administration and also reflect what is believed to demonstrate AAS dependency. More significantly, AAS prescribing after cessation adds the comorbid condition of hypogonadism to their already existing chronic illness. ASIH is critical towards any future planned use of AAS or similar compound to effect positive changes in muscle mass and muscle strength as well as an understanding for what has been termed anabolic steroid dependency. The further understanding and treatments that mitigate or prevent ASIH could contribute to androgen therapies for wasting associated diseases and stopping nonprescription AAS use. This paper proposes a unified hypothesis that the net effects for anabolic steroid administration must necessarily include the period after their cessation or ASIH.

An unusual case of vascular hypogonadism treated with clomiphene citrate and testosterone replacement.

Many male patients are discovered on screening to suffer from hypogonadism and age related hypogonadism is being increasingly recognized. However, secondary causes of hypogonadism should not be overlooked, especially in patients who may have concomitant morbidity as highlighted in this case. Our patient with vascular hypogonadism was treated with testosterone and clomiphene citrate in cycles; with a hope of improving not only androgen levels but overall pituitary function as there were co-existing endocrine pathologies of albeit primary hypothyroidism and low IGF-1 levels. Treatment with exogenous testosterone is fairly well established; but there is also increasing evidence of the effectiveness and short-term safety of clomiphene citrate in restoring not only biological levels but functional states in males as well. As such, we report an unusual case of a patient seen at our Men's Health & Andrology clinic in which both the cause of some otherwise unremarkable symptoms and the treatment, using a combination of clomiphene citrate and testosterone, were remarkable.

Preference for gender of health care provider in management of erectile dysfunction.

We investigated whether a preference by patients regarding the gender of a health care provider to manage erectile dysfunction (ED) may be a factor in the diagnosis and care of this condition, whose broader medical significance is an area of increasing interest. A brief questionnaire was completed by 1087 adult males in a primary care setting. The questionnaire explored provider gender preference and other possible biases. The prevalence of ED in the 40-69 age group in our population was 68.8%. The prevalence was 81% in the age group of 70 and more. Of those who reported having experienced ED, 51.5% had discussed it with a provider, and 28.1% had been treated. Approximately, 57% expressed no provider gender preference, regardless of history of ED. Of those who stated a preference, approximately 75% prefer male providers. However, also among those who state a preference, Hispanics are not as likely as non-Hispanics to prefer a male provider (P=0.03). Most believe that males and females are equally qualified to manage ED, but among those who have a different opinion, the gender perceived more favorably is male. The issue of privacy during the discussion of ED was also very important to the respondents in this study.

Risks of testosterone replacement therapy in ageing men.

Testosterone has been available to practitioners for several decades. However, testosterone prescriptions have increased in recent years partly because of the introduction of newer delivery systems that are topical and have good bioavailability. In the US alone, approximately 2 million prescriptions for testosterone were written in 2002. This represents a 30% increase from 2001 and a 170% increase from 1999. There has also been a 500% increase in prescription sales in the past 10 years. The rise in prescriptions may be in part due to the increasing recognition of hypogonadism in ageing males or andropause. Treatment relating to hypogonadism has relieved symptoms and improved the quality of life of many individuals. Epidemiological studies point toward an association with increased morbidity and mortality, with low testosterone states in ageing males. For example, there is a higher prevalence of depression, coronary heart disease, osteoporosis, fracture rates, frailty and even dementia with low testosterone states. Recently, there have been some concerns raised regarding the long-term safety of testosterone replacement therapy (TRT) from the Institute of Medicine. Current evidence suggests no causal relationship between prostate cancer and physiological dosing of testosterone, especially with careful selection and monitoring of patients. Cardiovascular risks have, overall, been neutral, although suggestions have been made that there are positive vasodilatory properties with testosterone. Mild eythrocytosis can be a common side effect of TRT, but thromboembolic events have rarely been reported in the literature. This paper addresses the evidence to date regarding the safety aspects of TRT. The medical-legal implications of TRT for men at this point in time is also discussed.

Coronary artery disease: comprehensive evaluation by cardiovascular magnetic resonance imaging.

Cardiac magnetic resonance (CMR) imaging has emerged as an important non-invasive cardiac imaging modality. A versatile technique, it has the potential for comprehensive evaluation of coronary artery disease (CAD): cardiac morphology and function, myocardial perfusion, myocardial viability, coronary artery visualisation and atherosclerotic plaque characterisation. Some of these techniques--ventricular function and myocardial viability assessment--have already made mainstream clinical impact. Other techniques have yielded promising initial results, and will become increasingly accepted with technical refinement in scanner hardware and software. This article reviews the current status of clinical CMR imaging for diagnosis of CAD.

Glagov remodeling of the atherosclerotic aorta demonstrated by cardiovascular magnetic resonance: the CORDA asymptomatic subject plaque assessment research (CASPAR) project.

BACKGROUND: Aortic atherosclerosis and coronary artery disease (CAD) are closely linked. Early detection of aortic atherosclerosis with the adoption of appropriate preventive measures may therefore help to reduce mortality and morbidity related to CAD. Arterial remodeling, by which the wall adapts to physiological or pathological insults by a change in vessel size, is being increasingly recognized as an important aspect of atherosclerosis. In this prospective longitudinal study we used cardiovascular magnetic resonance (CMR) to detect aortic plaque and to study aortic wall remodeling in asymptomatic subjects. METHODS: We recruited 175 healthy volunteers (49 years, 110 men) and documented their cardiovascular risk profile. Each subject underwent echocardiogram (ECG)-gated T1-weighted spin-echo imaging of the infrarenal abdominal aorta at baseline and after 2 years. FINDINGS: Of the 175 subjects who volunteered at baseline, CMR was successful in 174 (99%), with one (0.6%) failure due to claustrophobia. At 2 years, follow-up scanning was performed in 169 subjects (97%). Infrarenal aortic plaque was identified at baseline in nine (5.2%) subjects. This was reconfirmed in all nine (100%) cases at 2-year follow-up. No new cases of infrarenal plaque were identified at follow-up. The signal characteristics of the plaque on the subtracted images of the Dixon method indicate that all plaques were fibrous. In the nine subjects with infrarenal plaque, the total plaque burden increased as assessed by the total wall volume (561 to 677 mm3, p = 0.0063). The total vessel volume also increased (1737 to 1835 mm3, p = 0.031) but there was no change in the total luminal volume (1175 to 1157 mm3, p = 0.29). CONCLUSIONS: Cardiovascular magnetic resonance detects subclinical aortic atherosclerosis, can follow plaque burden over time, and confirms the presence of Glagov remodeling with preservation of the lumen despite progression of plaque. Cardiovascular magnetic resonance is well suited for the longitudinal follow-up of the general population with atherosclerosis, may help in the understanding of the natural history of atherosclerosis, and in particular may help determine factors to retard disease progression at an early stage.

Role of androgens in mild cognitive impairment and possible interventions during andropause.

Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like PET scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.

A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease.

The male aging process brings about declines in hormonal function including a gradual decline in bioavailable testosterone levels. Animal studies suggest that testosterone modulates cognitive function through enhancing acetylcholine release and up-modulation of nicotinic receptors. Tau protein deposition is also affected by androgen supplementation in animals. We hypothesize that testosterone replacement in elderly hypogonadal males may improve cognition, in particular the visual-spatial domain. Thirty-six male patients with a new diagnosis of Alzheimer's disease had their total and bioavailable testosterone levels measured. None of the patients had been on acetylcholinesterase inhibitors. Ten of the 36 patients (28%) were deemed biochemically hypogonadal (total testosterone < 240 ng/dl or 7 nmol/l). Five of the hypogonadal patients were randomized to testosterone and five to placebo. Initial Alzheimer's Disease Assessment Scale cognitive subscale (ADAScog) and Mini Mental Status Examination (MMSE) ranged from 31 to 19 and from 17 to 22, respectively. The clock drawing test (CDT) and the pentagon-tracing portion of the MMSE were used as measures of visual-spatial abilities. Normal prostate-specific antigen (PSA) levels were essential before treatment with intramuscular testosterone, 200 mg every 2 weeks. Measurement of testosterone, complete blood count, lipids, PSA and neuropsychological cognitive tests were repeated at 3, 6, 9 and 12 months of treatment. In the testosterone-treated group, levels of total testosterone increased from a mean of 126.4 ng/dl to 341 ng/dl or 3.6 nmol/l to 9.7 nmol/l (p = 0.11). Bioavailable testosterone also increased from a mean of 48.7 ng/dl to 142 ng/dl or 1.39 nmol/l to 4.05 nmol/l (p = 0.10). PSA levels were also elevated from a mean of 0.98 to 1.37 ng/ml (p = 0.07). ADAScog improved from a mean of 25 to 16.3 (p = 0.02); MMSE improved from a mean of 19.4 to 23.2 (p = 0.02), CDT also improved from 2.2 to 3.2 (p = 0.07). One patient stopped treatment because of hypersexual behavior. The placebo-treated group deteriorated gradually. This small pilot study performed in aging male patients suggests that testosterone could indeed improve cognition, including visual-spatial skills in mild to moderate Alzheimer's disease.

Role of androgens in mild cognitive impairment and possible interventions during andropause.

Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like positron emission tomography (PET) scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.

Impact of obesity on hypogonadism in the andropause.

Obesity is an issue that is increasingly affecting ageing men. With ageing, there is a decline in androgens as well. There are implications for the health of ageing men as a result of hypogonadism. Overall, there seems to be an inverse relationship between body mass index and testosterone levels, as is also demonstrated in our cross-sectional study. Obesity seems to depress the production of testosterone. It has been hypothesized that there is increased aromatization of testosterone to oestradiol and alteration of the hypothalamic-pituitary-adrenal axis in obese older men. Some hormones can affect obesity in ageing men including leptin, insulin, dehydroepiandrostenedione and growth hormone. The relationship of obesity to these hormones in ageing men will be reviewed. Testosterone replacement in ageing men can alter body composition whereby fat is exchanged for muscle. These studies will also be reviewed. Further studies in this field are recommended to evaluate long-term benefits and risks.