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Precision and personalized medicine, the process by which patient management is tailored to individual circumstances, are now terms that are familiar to cardiologists despite still being an emerging field. While precision medicine relies most often on the underlying biology/pathophysiology of a patient's condition, personalized medicine rely on digital biomarkers generated through algorithms. Given the complexity of the underlying data, these digital biomarkers are most often general through machine learning algorithms. There are a number of analytical considerations regarding the creation of digital biomarkers that are discussed in this review, including: data pre-processing, time dependency and gating, dimensionality reduction and novel methods both in the realm of supervised and unsupervised machine learning. Some of these considerations, such as sample size requirements and measurements of model performance are particularly challenging in small and heterogenous populations with rare outcomes like children with congenital heart disease. Finally, we review analytical considerations for the deployment of digital biomarkers in clinical settings, including the emerging field of clinical AI operations, computational needs for deployment, efforts to increase the explainability of AI, algorithmic drift and the needs for distributed surveillance and federated learning. We conclude this review by discussing a recent simulation study that shows that despite these analytical challenges and complications, the use of digital biomarkers in managing clinical care might have substantial benefits regarding individual patient outcomes.
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IMPORTANCE AND OBJECTIVES: The current medical paradigm of evidence-based medicine relies on clinical guidelines derived from randomized clinical trials (RCTs), but these guidelines often overlook individual variations in treatment effects. Approaches have been proposed to develop models predicting the effects of individualized management, such as predictive allocation, individualizing treatment allocation. It is currently unknown whether widespread implementation of predictive allocation could result in better population-level outcomes over guideline-based therapy. We sought to simulate the potential effect of predictive allocation using data from previously conducted RCTs. METHODS AND RESULTS: Data from 3 RCTs (positive trial, negative trial, trial stopped for futility) in pediatric cardiology were used in a computational simulation study to quantify the potential benefits of a personalized approach based on predictive allocation. Outcomes were compared when using a universal approach vs predictive allocation where each patient was allocated to the treatment associated with the lowest predicted probability of negative outcome. Compared to results from RCTs, predictive allocation yielded absolute risk reductions of 13.8% (95% confidence interval [CI] -1.9 to 29.5), 13.9% (95% CI 4.5-23.2), and 15.6% (95% CI 1.5-29.6), respectively, corresponding to a number needed to treat of 7.3, 7.2, and 6.4. The net benefit of predictive allocation was directly proportional to the performance of the prediction models and disappeared as model performance degraded below an area under the curve of 0.55. DISCUSSION: These findings highlight that predictive allocation could result in improved group-level outcomes, particularly when highly predictive models are available. These findings will need to be confirmed in simulations of other trials with varying conditions and eventually in RCTs of predictive vs guideline-based treatment allocation.
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Doenças Cardiovasculares , Simulação por Computador , Medicina de Precisão , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Doenças Cardiovasculares/terapia , Criança , Resultado do TratamentoRESUMO
;Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril-Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril-Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril-Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril-Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40-50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk.
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Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/farmacologia , Volume Sistólico/fisiologia , Tetrazóis/uso terapêutico , Tetrazóis/farmacologia , Qualidade de Vida , Função Ventricular Esquerda , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Resultado do Tratamento , Anti-Hipertensivos/uso terapêutico , Combinação de MedicamentosRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection not only affects the respiratory system but also induces coagulation abnormalities and thrombosis. We report a middle-aged woman who presented during the Covid-19 pandemic with sudden-onset acute left upper limb ischaemia of short duration, with no history of dry cough, breathlessness or fever, and tested positive on TrueNAT for SARS-CoV-2. Later, she developed deep venous thrombosis of the right lower limb during isolation in the hospital.
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COVID-19 , Trombose Venosa , Pessoa de Meia-Idade , Feminino , Humanos , COVID-19/complicações , COVID-19/diagnóstico , SARS-CoV-2 , Pandemias , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Perna (Membro)RESUMO
Due to awareness and benefits of goat rearing in developing economies, goats' significance is increasing. Unfortunately, these ruminants are threatened via multiple bacterial pathogens such as enteropathogenic Escherichia coli (EPEC). In goat kids and lambs, EPEC causes gastrointestinal disease leading to substantial economic losses for farmers and may also pose a threat to public health via the spread of zoonotic diseases. Management of infection is primarily based on antibiotics, but the need for new therapeutic measures as an alternative to antibiotics is becoming vital because of the advent of antimicrobial resistance (AMR). The prevalence of EPEC was established using bfpA gene, uspA gene and Stx1 gene, followed by phylogenetic analysis using Stx1 gene. The lytic activity of the isolated putative coliphages was tested on multi-drug resistant strains of EPEC. It was observed that a PCR based approach is more effective and rapid as compared to phenotypic tests of Escherichia coli virulence. It was also established that the isolated bacteriophages exhibited potent antibacterial efficacy in vitro, with some of the isolates (16%) detected as T4 and T4-like phages based on gp23 gene. Hence, bacteriophages as therapeutic agents may be explored as an alternative to antibiotics in managing public, livestock and environmental health in this era of AMR.
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Bacteriófagos , Escherichia coli Enteropatogênica , Infecções por Escherichia coli , Proteínas de Escherichia coli , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriófagos/genética , Escherichia coli Enteropatogênica/genética , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/genética , Cabras/microbiologia , Filogenia , OvinosAssuntos
Alopecia , Líquen Plano , Alopecia/epidemiologia , Estudos Transversais , Feminino , Fibrose , Humanos , Reino Unido/epidemiologiaRESUMO
Crohn's disease is among the chronic inflammatory bowel diseases that impact the gastrointestinal tract. Understanding and predicting the severity of inflammation in real-time settings is critical to disease management. Extant literature has primarily focused on studies that are conducted in clinical trial settings to investigate the impact of a drug treatment on the remission status of the disease. This research proposes an analytics methodology where three different types of prediction models are developed to predict and to explain the severity of inflammation in patients diagnosed with Crohn's disease. The results show that machine-learning-based analytic methods such as gradient boosting machines can predict the inflammation severity with a very high accuracy (area under the curve = 92.82%), followed by regularized regression and logistic regression. According to the findings, a combination of baseline laboratory parameters, patient demographic characteristics, and disease location are among the strongest predictors of inflammation severity in Crohn's disease patients.
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Doença de Crohn/fisiopatologia , Registros Eletrônicos de Saúde , Inflamação , Proteína C-Reativa/análise , Mineração de Dados , Previsões/métodos , Humanos , Modelos Logísticos , Aprendizado de Máquina , Estados UnidosRESUMO
Hospital readmission is one of the critical metrics used for measuring the performance of hospitals. The HITECH Act imposes penalties when patients are readmitted to hospitals if they are diagnosed with one of the six conditions mentioned in the Act. However, patients diagnosed with lupus are the sixth highest in terms of rehospitalization. The heterogeneity in the disease and patient characteristics makes it very hard to predict rehospitalization. This research utilizes deep learning methods to predict rehospitalization within 30 days by extracting the temporal relationships in the longitudinal EHR clinical data. Prediction results from deep learning methods such as LSTM are evaluated and compared with traditional classification methods such as penalized logistic regression and artificial neural networks. The simple recurrent neural network method and its variant, gated recurrent unit network, are also developed and validated to compare their performance against the proposed LSTM model. The results indicated that the deep learning method RNN-LSTM has a significantly better performance (with an AUC of .70) compared to traditional classification methods such as ANN (with an AUC of 0.66) and penalized logistic regression (with an AUC of 0.63). The rationale for the better performance of the deep learning method may be due to its ability to leverage the temporal relationships of the disease state in patients over time and to capture the progression of the disease-relevant clinical information from patients' prior visits is carried forward in the memory, which may have enabled the higher predictability for the deep learning methods.
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Aprendizado Profundo , Lúpus Eritematoso Sistêmico/terapia , Modelos Biológicos , Redes Neurais de Computação , Readmissão do Paciente , Feminino , Humanos , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Valor Preditivo dos TestesRESUMO
OBJECTIVES: This study investigated the capability of spectral parameters, extracted by frequency domain analysis of photoacoustic signals, to differentiate among malignant, benign, and normal thyroid tissue. METHODS: We acquired multiwavelength photoacoustic images of freshly excised thyroid specimens collected from 50 patients who underwent thyroidectomy after having a diagnosis of suspected thyroid lesions. A thyroid cytopathologist marked histologic slides of each tissue specimen. These marked slides were used as ground truth to identify the regions of interest (ROIs) corresponding to malignant, benign, and normal thyroid tissue. Three spectral parameters: namely, slope, midband fit, and intercept, were extracted from photoacoustic signals corresponding to different ROIs. RESULTS: Spectral parameters were extracted from a total of total of 65 ROIs. According to the ground truth, 12 of 65 ROIs belonged to malignant thyroids; 28 of 65 ROIs belonged to benign thyroids; and 25 of 65 ROIs belonged to normal thyroids. Besides slope, the other 2 spectral parameters and grayscale photoacoustic image pixel values were found to be significantly different (P < .05) between malignant and normal thyroids. Between benign and normal thyroids, all 3 spectral parameters and photoacoustic pixel values were significantly different (P < .05). CONCLUSIONS: Preliminary results of our ex vivo human thyroid study show that the spectral parameters extracted from radiofrequency photoacoustic signals as well as the pixel values of 2-dimensional photoacoustic images can be used for differentiating among malignant, benign, and normal thyroid tissue.
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Técnicas Fotoacústicas/métodos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Glândula Tireoide/cirurgiaRESUMO
OBJECTIVES: The purpose of this study was to investigate the feasibility of differentiating malignant prostate from benign prostatic hyperplasia (BPH) and normal prostate tissue by performing frequency domain analysis of photoacoustic images acquired at 2 different wavelengths. METHODS: We performed multiwavelength photoacoustic imaging on freshly excised human prostate specimens taken from a total of 30 patients undergoing prostatectomy for biopsy-confirmed prostate cancer. Histologic slides marked by a genitourinary pathologist were used as ground truth to define regions of interest (ROIs) in the photoacoustic images. Primarily, 3 different prostate tissue categories, namely malignant, BPH, and normal, were considered, while a fourth category named nonmalignant was formed by combining the ROIs corresponding to BPH and normal tissue together. We extracted 3 spectral parameters, namely slope, midband fit, and intercept, from power spectra of the radiofrequency photoacoustic signals corresponding to the 3 primary tissue categories. RESULTS: We analyzed data from 53 ROIs selected from the photoacoustic images of 30 patients. According to the histopathologic analysis, 19 ROIs were malignant, 8 were BPH, and 26 were normal. All the 3 spectral parameters and C-scan grayscale photoacoustic image pixel values were found to be significantly different (P < .01) between malignant and nonmalignant prostate as well as malignant and normal prostate. CONCLUSIONS: Preliminary results of our ex vivo human prostate study suggest that spectral parameters obtained by performing frequency domain analysis of photoacoustic signals can be used to differentiate between malignant and nonmalignant prostate.
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Técnicas Fotoacústicas/métodos , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , Ultrassonografia/métodos , Diagnóstico Diferencial , Estudos de Viabilidade , Humanos , Masculino , Próstata/diagnóstico por imagem , Próstata/cirurgia , Prostatectomia , Hiperplasia Prostática/diagnóstico por imagem , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Reprodutibilidade dos TestesRESUMO
PURPOSE: We aimed to explore the hypothesis that early subclinical cardiac chamber dysfunction secondary to tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma could be signaled by abnormal cardiac mechanics demonstrated by velocity vector imaging. METHODS: Echocardiographic images were acquired from the apical views in 23 metastatic renal cell carcinoma patients. All patients had baseline and at least a 3-month follow-up echocardiogram after receiving TKI therapy. Subendocardial borders of all the cardiac chambers were traced to obtain volumetric and deformation indices. RESULTS: Mean age was 67 ± 9 years with 92% men. The right ventricle peak systolic global longitudinal strain (GLÉ) and strain rate were significantly lower after TKIs (-23.49 ± 5.1 versus -19.81 ± 5.5, p = 0.002 and -1.52 ± 0.52 versus -1.24 ± 0.35 p = 0.02, respectively). LV GLÉ was not statistically different. Volumetric and deformation indices showed a minimal decrease of the right atrium reservoir and conduit functions, and no significant changes of left atrial function. CONCLUSIONS: The right heart exhibited greater strain changes than the left heart after TKI treatment. The implications of these findings and their potential significance warrant further work.
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Carcinoma de Células Renais/tratamento farmacológico , Ecocardiografia/métodos , Átrios do Coração/fisiopatologia , Ventrículos do Coração/fisiopatologia , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Disfunção Ventricular/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/secundário , Ecocardiografia Doppler , Feminino , Seguimentos , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/efeitos dos fármacos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/efeitos dos fármacos , Humanos , Neoplasias Renais/complicações , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Volume Sistólico/efeitos dos fármacos , Sístole , Disfunção Ventricular/diagnóstico , Disfunção Ventricular/fisiopatologiaRESUMO
BACKGROUND: Trastuzumab has substantially improved overall survival and reduced the risk of disease recurrence in patients with human epidermal growth factor receptor type II (HER-II)-positive breast cancer. However, this benefit may be at the increased risk of cardiotoxicity. We aimed to explore the early subclinical left and right ventricular as well as atrial dysfunction, in trastuzumab-treated patients with HER-II-positive breast cancer, using velocity vector imaging. METHODS: Echocardiography images were acquired in 50 patients with HER-II-positive breast cancer undergoing trastuzumab therapy. All patients had baseline and 3-6 months and 12-15 months of follow-up echocardiograms after initiation of trastuzumab therapy. Subendocardial borders of all the cardiac chambers were traced from the apical views to obtain volumetric and deformation indices. RESULTS: Mean age was 60 ± 13 years. Left ventricular (LV) ejection fraction as well as conventional indices of right ventricular (RV) function did not change with trastuzumab. The RV peak systolic global longitudinal strain (GLε) significantly decreased (-24.53 ± 6.03 vs. -21.28 ± 5.11 vs. -21.84 ± 5.15, baseline vs. first and second follow-ups, P = 0.01). LV peak systolic GLε was reduced by 1.19 at early follow-up (P < 0.05). Left atrial reservoir and booster pump functions as well as right atrial reservoir function were reduced through follow-up as well. CONCLUSIONS: The RV exhibited greater change in strain after trastuzumab treatment when compared to the LV. Atria function was reduced by trastuzumab as well. The repercussion of these findings and their potential implication will warrant further study.
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Neoplasias da Mama/tratamento farmacológico , Ecocardiografia/métodos , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Disfunção Ventricular/induzido quimicamente , Disfunção Ventricular/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/metabolismo , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/efeitos dos fármacos , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Volume Sistólico/efeitos dos fármacos , Resultado do TratamentoRESUMO
Hypoxia is a well-known threat to neuronal cells and triggers the pathophysiological syndromes in extreme environments such as high altitudes and traumatic conditions such as stroke. Among several prophylactic molecules proven suitable for ameliorating free radical damage, NAP (an octapeptide with initial amino acids: asparagine/N, alanine/A, and proline/P) can be considered superlative, primarily due to its high permeability into brain through blood-brain barrier and observed activity at femtomolar concentrations. Several mechanisms of action of NAP have been hypothesized for its protective role during hypoxia, yet any distinct mechanism is unknown. Oxidative stress is advocated as the leading event in hypoxia; we, therefore, investigated the regulation of key antioxidant genes to understand the regulatory role of NAP in providing neuroprotection. Primary neuronal culture of rat was subjected to cellular hypoxia by limiting the oxygen concentration to 0.5% for 72 h and observing the prophylactic efficacies of 15fM NAP by conventional cell death assays using flow cytometry. We performed real-time quantitative polymerase chain reaction to comprehend the regulatory mechanism. Further, we validated the significantly regulated candidates by enzyme assays and immunoblotting. In the present study, we report that NAP regulates a major clad of cellular antioxidants and there is an involvement of more than one route of action in neuroprotection during hypoxia.
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Antioxidantes/metabolismo , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Oligopeptídeos/farmacologia , Estresse Oxidativo/genética , Animais , Hipóxia Celular , Células Cultivadas , Regulação Enzimológica da Expressão Gênica , Hipocampo/enzimologia , Hipocampo/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis defined by heterogeneous multiorgan involvement. Due to the rarity of this disease strong evidence-based therapies have yet to be established and prognosis has previously been considered to be poor, with more than half of patients dying within 3 years of initial presentation. We describe an 86-year-old woman with a 34-year history of extensive cutaneous and internal nodules with typical pathological and immunophenotypical (CD68(+) /CD1a(-) ) features of ECD without evidence of the BRAF V600E mutation. The cosmetic appearance of cutaneous nodules and hoarse voice caused by vocal cord nodules has been managed surgically. More aggressive therapies reported for ECD were trialled for this patient, such as radiotherapy and interferon-α, with no response. This case demonstrates a relatively good prognosis in ECD that has been managed conservatively.
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Doença de Erdheim-Chester/patologia , Doenças da Boca/patologia , Nódulos Pulmonares Múltiplos/patologia , Doenças Faríngeas/patologia , Dermatopatias/patologia , Idoso de 80 Anos ou mais , Doenças Ósseas/diagnóstico por imagem , Doença Crônica , Feminino , Humanos , Imageamento por Ressonância Magnética , Imagem Multimodal , Cintilografia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The purpose of this study was to validate whether ex vivo multispectral photoacoustic imaging can be used to differentiate malignant tissue, benign nodules, and normal human thyroid tissue. SUBJECTS AND METHODS: Fifty patients undergoing thyroidectomy because of thyroid lesions participated in this study. Multispectral photoacoustic imaging was performed on surgically excised thyroid tissue, and chromophore images that represented optical absorption of deoxyhemoglobin, oxyhemoglobin, lipid, and water were reconstructed. After the imaging procedure, the pathologist marked malignant tissue, benign nodules, and normal regions on histopathologic slides, and digital images of the marked histopathologic slides were obtained. The histopathologic images were coregistered with chromophore images. Areas corresponding to malignant tissue, benign nodules, and normal tissue were defined on the chromophore images. Pixel values within each area were averaged to determine the mean intensities of deoxyhemoglobin, oxyhemoglobin, lipid, and water. RESULTS: There was a statistically significant difference between malignant and benign nodules with respect to mean intensity of deoxyhemoglobin (p = 0.014). There was a difference between malignant and normal tissue in mean intensity of deoxyhemoglobin (p = 0.003), lipid (p = 0.001), and water (p < 0.0001). A difference between benign nodules and normal tissue was found in mean intensity of oxyhemoglobin (p < 0.0001), lipid (p < 0.0001), and water (p < 0.0001). The sensitivity, specificity, and positive and negative predictive values of the system tested in differentiating malignant from nonmalignant thyroid tissue were 69.2%, 96.9%, 81.8%, and 93.9%. CONCLUSION: The preliminary results of this ex vivo human thyroid study suggest that multispectral photoacoustic imaging can be used to differentiate malignant and benign nodules and normal human thyroid tissue.
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Técnicas de Imagem por Elasticidade/métodos , Técnicas Fotoacústicas/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Adulto , Idoso , Biomarcadores/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Projetos Piloto , Neoplasias da Glândula Tireoide/metabolismo , Tireoidectomia , Resultado do Tratamento , Adulto JovemRESUMO
Cerium oxide nanoparticles (CNPs) of spherical shape have unique antioxidant capacity primarily due to alternating + 3 and + 4 oxidation states and crystal defects. Several studies revealed the protective efficacies of CNPs in cells and tissues against the oxidative damage. However, its effect on mitochondrial functioning, downstream effectors of radical burst and apoptosis remains unknown. In this study, we investigated whether CNPs treatment could protect the primary cortical cells from loss of mitochondrial membrane potential (Δψm) and Δψm-dependent cell death. CNPs with spherical morphology and size range 7-10 nm were synthesized and utilized at a concentration of 25 nM on primary neuronal culture challenged with 50 µM of hydrogen peroxide (H2O2). We showed that optimal dose of CNPs minimized ROS content of the cells and also curbed related surge in cellular calcium flux. Importantly, CNPs treatment prevented apoptotic loss of cell viability. Reduction in the apoptosis could be successfully attributed to the maintenance of Δψm and restoration of major redox equivalents NADH/NAD(+) ratio and cellular ATP. These findings, therefore, suggest possible route of CNPs protective efficacies in primary cortical culture.
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Apoptose/efeitos dos fármacos , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Cério/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/metabolismo , Cério/química , Cães , Relação Dose-Resposta a Droga , Peróxido de Hidrogênio/farmacologia , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Propriedades de SuperfícieRESUMO
OBJECTIVE: The objective of this study is to validate if ex-vivo multispectral photoacoustic (PA) imaging can differentiate between malignant prostate tissue, benign prostatic hyperplasia (BPH), and normal human prostate tissue. MATERIALS AND METHODS: Institutional Review Board's approval was obtained for this study. A total of 30 patients undergoing prostatectomy for biopsy-confirmed prostate cancer were included in this study with informed consent. Multispectral PA imaging was performed on surgically excised prostate tissue and chromophore images that represent optical absorption of deoxyhemoglobin (dHb), oxyhemoglobin (HbO2), lipid, and water were reconstructed. After the imaging procedure is completed, malignant prostate, BPH and normal prostate regions were marked by the genitourinary pathologist on histopathology slides and digital images of marked histopathology slides were obtained. The histopathology images were co-registered with chromophore images. Region of interest (ROI) corresponding to malignant prostate, BPH and normal prostate were defined on the chromophore images. Pixel values within each ROI were then averaged to determine mean intensities of dHb, HbO2, lipid, and water. RESULTS: Our preliminary results show that there is statistically significant difference in mean intensity of dHb (P < 0.0001) and lipid (P = 0.0251) between malignant prostate and normal prostate tissue. There was difference in mean intensity of dHb (P < 0.0001) between malignant prostate and BPH. Sensitivity, specificity, positive predictive value, and negative predictive value of our imaging system were found to be 81.3%, 96.2%, 92.9% and 89.3% respectively. CONCLUSION: Our preliminary results of ex-vivo human prostate study suggest that multispectral PA imaging can differentiate between malignant prostate, BPH and normal prostate tissue.