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Rationale: Idiopathic pulmonary fibrosis (IPF) affects the subpleural lung but is considered to spare small airways. Micro-computed tomography (micro-CT) studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. Objectives: In this study, EB-OCT was used to evaluate small airways in early IPF and control subjects in vivo. Methods: EB-OCT was performed in 12 subjects with IPF and 5 control subjects (matched by age, sex, smoking history, height, and body mass index). Subjects with IPF had early disease with mild restriction (FVC: 83.5% predicted), which was diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for usual interstitial pneumonia present) and less affected (some but not all criteria for usual interstitial pneumonia present). Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. Measurements and Main Results: Compared with the number of bronchioles in control subjects (mean = 11.2/cm3; SD = 6.2), there was significant bronchiole reduction in subjects with IPF (42% loss; mean = 6.5/cm3; SD = 3.4; P = 0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; P < 0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; P = 0.024) sites. Stereology metrics showed that IPF-affected small airways were significantly larger, more distorted, and more irregular than in IPF-less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (P = 0.36-1.0). Conclusions: EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30% and 50%), even in areas minimally affected by disease, compared with matched control subjects. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.
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Broncoscopia , Fibrose Pulmonar Idiopática , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Masculino , Feminino , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/patologia , Pessoa de Meia-Idade , Idoso , Broncoscopia/métodos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Estudos de Casos e ControlesRESUMO
Rationale: Early, accurate diagnosis of interstitial lung disease (ILD) informs prognosis and therapy, especially in idiopathic pulmonary fibrosis (IPF). Current diagnostic methods are imperfect. High-resolution computed tomography has limited resolution, and surgical lung biopsy (SLB) carries risks of morbidity and mortality. Endobronchial optical coherence tomography (EB-OCT) is a low-risk, bronchoscope-compatible modality that images large lung volumes in vivo with microscopic resolution, including subpleural lung, and has the potential to improve the diagnostic accuracy of bronchoscopy for ILD diagnosis. Objectives: We performed a prospective diagnostic accuracy study of EB-OCT in patients with ILD with a low-confidence diagnosis undergoing SLB. The primary endpoints were EB-OCT sensitivity/specificity for diagnosis of the histopathologic pattern of usual interstitial pneumonia (UIP) and clinical IPF. The secondary endpoint was agreement between EB-OCT and SLB for diagnosis of the ILD fibrosis pattern. Methods: EB-OCT was performed immediately before SLB. The resulting EB-OCT images and histopathology were interpreted by blinded, independent pathologists. Clinical diagnosis was obtained from the treating pulmonologists after SLB, blinded to EB-OCT. Measurements and Main Results: We enrolled 31 patients, and 4 were excluded because of inconclusive histopathology or lack of EB-OCT data. Twenty-seven patients were included in the analysis (16 men, average age: 65.0 yr): 12 were diagnosed with UIP and 15 with non-UIP ILD. Average FVC and DlCO were 75.3% (SD, 18.5) and 53.5% (SD, 16.4), respectively. Sensitivity and specificity of EB-OCT was 100% (95% confidence interval, 75.8-100.0%) and 100% (79.6-100%), respectively, for both histopathologic UIP and clinical diagnosis of IPF. There was high agreement between EB-OCT and histopathology for diagnosis of ILD fibrosis pattern (weighted κ: 0.87 [0.72-1.0]). Conclusions: EB-OCT is a safe, accurate method for microscopic ILD diagnosis, as a complement to high-resolution computed tomography and an alternative to SLB.
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Broncoscopia/métodos , Broncoscopia/normas , Confiabilidade dos Dados , Fibrose Pulmonar Idiopática/diagnóstico , Tomografia de Coerência Óptica/métodos , Tomografia de Coerência Óptica/normas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is essential to inform prognosis and treatment. In 2018, the ATS/ERS/JRS/ALAT and Fleischner Society released new diagnostic guidelines for usual interstitial pneumonitis (UIP)/IPF, adding Probable UIP as a CT category based on prior studies demonstrating this category had relatively high positive predictive value (PPV) for histopathologic UIP/Probable UIP. This study applies the 2018 ATS/ERS/JRS/ALAT and Fleischner Society guidelines to determine test characteristics of CT categories in academic clinical practice. METHODS: CT and histopathology were evaluated by three thoracic radiologists and two thoracic pathologists. Comparison of consensus categorization by the 2018 ATS and Fleischner Society guidelines by CT and histopathology was performed. RESULTS: Of patients with CT UIP, 87% (PPV, 95% CI: 60-98%) had histopathologic UIP with 97% (CI: 90-100%) specificity. Of patients with CT Probable UIP, 38% (PPV, CI: 14-68%) had histopathologic UIP and 46% (PPV, CI: 19-75%) had either histopathologic UIP or Probable UIP, with 88% (CI: 77-95%) specificity. Patients with CT Indeterminate and Alternative Diagnosis had histopathologic UIP in 27% (PPV, CI: 6-61%) and 21% (PPV, CI: 11-33%) of cases with specificities of 90% (CI: 80-96%) and 25% (CI: 16-37%). Interobserver variability (kappa) between radiologists ranged 0.32-0.81. CONCLUSIONS: CT UIP and Probable UIP have high specificity for histopathologic UIP, and CT UIP has high PPV for histopathologic UIP. PPV of CT Probable UIP was 46% for combined histopathologic UIP/Probable UIP. Our results indicate that additional studies are needed to further assess and refine the guideline criteria to improve classification performance.
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Fibrose Pulmonar Idiopática/diagnóstico , Pulmão/diagnóstico por imagem , Pulmão/patologia , Guias de Prática Clínica como Assunto/normas , Tomografia Computadorizada por Raios X/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/normas , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/patologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sociedades Médicas , Adulto JovemAssuntos
Doenças Pulmonares Intersticiais , Tomografia de Coerência Óptica , Tomografia de Coerência Óptica/métodos , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/patologia , Broncoscopia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Pulmão/diagnóstico por imagem , Pulmão/patologia , IdosoRESUMO
Purpose To assess transvaginal coregistered photoacoustic tomography (PAT) and pulse-echo US for diagnosis of ovarian cancer based on functional parameters provided by PAT. Materials and Methods Between February 2017 and December 2017, 26 ovarian masses from 16 participants were successfully imaged in vivo by multispectral photoacoustic imaging, including nine invasive epithelial ovarian cancers (six serous carcinomas and three endometroid adenocarcinomas), three other tumors (two borderline serous tumors and one sex cord-stromal tumor), and 14 benign and normal (hereafter referred to as benign/normal) ovaries. The relative total hemoglobin concentration (rHbT) and mean oxygen saturation (sO2) shown at PAT were used to characterize the ovaries identified at US. Results The average rHbT was 1.9 times higher for invasive epithelial cancers than for the benign/normal ovaries (P = .01). Additionally, the rHbT distribution was extensive in invasive epithelial cancers, but was scattered in benign/normal ovaries. However, the rHbT of two borderline serous tumors and one stromal tumor was in the same range as that of benign/normal ovaries. The mean sO2 of invasive epithelial cancers, and of the borderline and stromal tumors, was 8.2% lower than that of benign/normal ovaries (P = .003). Discussion Invasive epithelial ovarian cancers showed higher and extensive tumor vascularity and lower oxygen saturation than benign and normal ovaries. Two borderline noninvasive serous and one stromal tumor showed low oxygen saturation compared with benign and normal ovaries. ©RSNA, 2018 Online supplemental material is available for this article.
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Neoplasias Ovarianas/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Ultrassonografia/métodos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Ovário/diagnóstico por imagem , Projetos PilotoRESUMO
BACKGROUND: Vaping, including the use of electronic cigarettes (e-cigarettes), has become increasingly prevalent, yet the associated long-term health risks are largely unknown. Given the prevalence of use, particularly among adolescents early in their lifespan, it is vital to understand the potential chronic pathologic sequelae of vaping. METHODS: We present the cases of four patients with chronic lung disease associated with e-cigarette use characterized by clinical evaluation, with pulmonary function tests (PFTs), chest high-resolution computed tomography (HRCT), endobronchial optical coherence tomography (EB-OCT) imaging, and histopathologic assessment. RESULTS: Each patient presented with shortness of breath and chest pain in association with a 3- to 8-year history of e-cigarette use, with mild progressive airway obstruction on PFTs and/or chest HRCT findings demonstrating evidence of air trapping and bronchial wall thickening. EB-OCT imaging performed in two patients showed small airway-centered fibrosis with bronchiolar narrowing and lumen irregularities. The predominant histopathologic feature on surgical lung biopsy was small airway-centered fibrosis, including constrictive bronchiolitis and MUC5AC overexpression in all patients. Patients who ceased vaping had a partial, but not complete, reversal of disease over 1 to 4 years. CONCLUSIONS: After thorough evaluation for other potential etiologies, vaping was considered to be the most likely common causal etiology for all patients due to the temporal association of symptomatic chronic lung disease with e-cigarette use and partial improvement in symptoms after e-cigarette cessation. In this series, we associate the histopathologic pattern of small airway-centered fibrosis, including constrictive bronchiolitis, with vaping, potentially defining a clinical and pathologic entity associated with e-cigarette use. (Funded in part by the National Institutes of Health.).
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Adequate tumor yield in core-needle biopsy (CNB) specimens is essential in lung cancer for accurate histological diagnosis, molecular testing for therapeutic decision-making, and tumor biobanking for research. Insufficient tumor sampling in CNB is common, primarily due to inadvertent sampling of tumor-associated fibrosis or atelectatic lung, leading to repeat procedures and delayed diagnosis. Currently, there is no method for rapid, non-destructive intraprocedural assessment of CNBs. Polarization-sensitive optical coherence tomography (PS-OCT) is a high-resolution, volumetric imaging technique that has the potential to meet this clinical need. PS-OCT detects endogenous tissue properties, including birefringence from collagen, and degree of polarization uniformity (DOPU) indicative of tissue depolarization. Here, PS-OCT birefringence and DOPU measurements were used to quantify the amount of tumor, fibrosis, and normal lung parenchyma in 42 fresh, intact lung CNB specimens. PS-OCT results were compared to and validated against matched histology in a blinded assessment. Linear regression analysis showed strong correlations between PS-OCT and matched histology for quantification of tumors, fibrosis, and normal lung parenchyma in CNBs. PS-OCT distinguished CNBs with low tumor content from those with higher tumor content with high sensitivity and specificity. This study demonstrates the potential of PS-OCT as a method for rapid, non-destructive, label-free intra-procedural tumor yield assessment.
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The current gold standard diagnostic test for colorectal cancer remains histological inspections of endoluminal neoplasia in biopsy specimens. However, biopsy site selection requires visual inspection of the bowel, typically with a white-light endoscope. Therefore, this technique is poorly suited to detect small or innocuous-appearing lesions. We hypothesize that an alternative modality-multiwavelength spatial frequency domain imaging (SFDI)-would be able to differentiate various colorectal neoplasia from normal tissue. In this ex vivo study of human colorectal tissues, we report the optical absorption and scattering signatures of normal, adenomatous polyp and cancer specimens. An abnormal vs. normal adaptive boosting (AdaBoost) classifier is trained to dichotomize tissue based on SFDI imaging characteristics, and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95 is achieved. We conclude that AdaBoost-based multiwavelength SFDI can differentiate abnormal from normal colorectal tissues, potentially improving endoluminal screening of the distal gastrointestinal tract in the future.
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Neoplasias Colorretais , Testes Diagnósticos de Rotina , Neoplasias Colorretais/diagnóstico por imagem , Diagnóstico por Imagem , Humanos , Curva ROCRESUMO
An optimized hand-held photoacoustic and ultrasound probe suitable for endo-cavity tumor subsurface imaging was designed and evaluated. Compared to previous designs, the prototype probe, consisting of four 1 mm multi-mode optical fibers attached with 1.5 mm diameter ball-shaped fiber tips sandwiched between a transvaginal ultrasound transducer and a custom-made sheath, demonstrated a higher light output and better beam homogeneity on tissue subsurface. The output power and fluence profile were simulated for different design parameters. A camera recorded fluence profiles through calibrated intralipid solution at various imaging depths. The light delivery efficiency was experimentally compared with and without the ball lenses, based on ex-vivo imaging of human colorectal cancer and in-vivo imaging of a palmar vein proximal to the human wrist. The simulations and experiments demonstrated that ball-shaped fiber tip design can achieve homogeneous fluence distribution on tissue subsurface with acceptable light output efficiency, suggesting its clinical potential for in-vivo endo-cavity imaging.
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We report in this pilot study the diagnostic results of in vivo imaging of patients with ovarian lesions, using a co-registered photoacoustic and ultrasound (PAT/US) system. A total of 39 ovaries from 24 patients were imaged in vivo. PAT functional features, i.e., blood oxygen saturation (sO2) and relative total hemoglobin (rHbT), PAT image features, and PAT spectral features within a region of interest (ROI) in each ovarian tissue were extracted. To select the significant features, a t-test on each feature was performed, and the independent predictors were determined by evaluating correlation between each pair of predictors. To classify the ovarian lesions, we employed a generalized linear model (GLM) and a support vector machine (SVM). We used these classifiers first to distinguish benign/normal lesions from ovaries with invasive epithelial tumors and then to separate normal/benign lesions from all types of ovarian tumors. We developed classifiers once by inclusion of PAT functional features to assess the best diagnostic performance of the classifiers when multiple wavelengths data are available. Second time, we excluded the PAT functional features from the features set to evaluate the best diagnostic performance if only a single wavelength is available. Our results show that using functional features improves the classification performance, especially for distinguishing normal/benign ovarian lesions from all types of tumors. In this case, an area under ROC curve (AUC) of 0.92, 0.93 of testing data was achieved using a GLM and SVM classifier when functional features were included in the feature set while excluding these features resulted in an AUC of 0.89, 0.92, respectively.
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Colorectal cancer is the second most common malignancy diagnosed globally. Critical gaps exist in diagnostic and surveillance imaging modalities for colorectal neoplasia. Although prior studies have demonstrated the capability of photoacoustic imaging techniques to differentiate normal from neoplastic tissue in the gastrointestinal tract, evaluation of deep tissue with a fast speed and a large field of view remains limited. To investigate the ability of photoacoustic technology to image deeper tissue, we conducted a pilot study using a real-time co-registered photoacoustic tomography (PAT) and ultrasound (US) system. A total of 23
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Neoplasias Colorretais/diagnóstico por imagem , Técnicas Fotoacústicas , Ultrassonografia , Adenocarcinoma/diagnóstico por imagem , Área Sob a Curva , Pólipos do Colo/diagnóstico por imagem , Trato Gastrointestinal/diagnóstico por imagem , Hemoglobinas/análise , Humanos , Modelos Estatísticos , Imagem Multimodal , Projetos Piloto , Curva ROC , Análise de Regressão , Máquina de Vetores de SuporteRESUMO
Colorectal cancer diagnosis currently relies on histological detection of endoluminal neoplasia in biopsy specimens. However, clinical visual endoscopy provides no quantitative subsurface cancer information. In this ex vivo study of nine fresh human colon specimens, we report the first use of quantified subsurface scattering coefficient maps acquired by swept-source optical coherence tomography to reveal subsurface abnormities. We generate subsurface scattering coefficient maps with a novel wavelet-based-curve-fitting method that provides significantly improved accuracy. The angular spectra of scattering coefficient maps of normal tissues exhibit a spatial feature distinct from those of abnormal tissues. An angular spectrum index to quantify the differences between the normal and abnormal tissues is derived, and its strength in revealing subsurface cancer in ex vivo samples is statistically analyzed. The study demonstrates that the angular spectrum of the scattering coefficient map can effectively reveal subsurface colorectal cancer and potentially provide a fast and more accurate diagnosis.
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Colo/diagnóstico por imagem , Neoplasias Colorretais/patologia , Tomografia de Coerência Óptica/métodos , Colo/patologia , Neoplasias Colorretais/diagnóstico por imagem , Humanos , Sensibilidade e Especificidade , Tomografia de Coerência Óptica/normasRESUMO
Ovarian cancer is a heterogeneous disease at the molecular and histologic level. Optical coherence tomography (OCT) is able to map ovarian tissue optical properties and heterogeneity, which has been proposed as a feature to aid in diagnosis of ovarian cancer. In this manuscript, depth-resolved en face scattering maps of malignant ovaries, benign ovaries, and benign fallopian tubes obtained from 20 patients are provided to visualize the heterogeneity of ovarian tissues. Six features are extracted from histograms of scattering maps. All features are able to statistically distinguish benign from malignant ovaries. Two prediction models were constructed based on these features: a logistic regression model (LR) and a support vector machine (SVM). The optimal set of features is mean scattering coefficient and scattering map entropy. The LR achieved a sensitivity and specificity of 97.0% and 97.8%, and SVM demonstrated a sensitivity and specificity of 99.6% and 96.4%. Our initial results demonstrate the feasibility of using OCT as an "optical biopsy tool" for detecting the microscopic scattering changes associated with neoplasia in human ovarian tissue.
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Neoplasias Ovarianas/patologia , Ovário/patologia , Tomografia de Coerência Óptica , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Ovarianas/diagnóstico por imagem , Ovário/diagnóstico por imagemRESUMO
We present a low-cost, compact, and multispectral spatial frequency domain imaging prototype. Illumination components, including 9 LEDs (660 nm - 950 nm) placed on a custom-designed printed circuit board, linear and rotational motors, a printed sinusoidal pattern, and collimation and projection optics as well as the detection components are incorporated in a compact custom-designed 3D-printed probe. Reconstruction of absorption and reduced scattering coefficients is evaluated via imaging tissue mimicking phantoms and potentials of the probe for biological tissue imaging are evaluated via imaging human ovarian tissue ex vivo.
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About 85-90% of all ovarian cancers are carcinomas; these manifest clinically as mass-forming epithelial proliferations involving the ovary. In this study, a visible light spatial frequency domain imaging (SFDI) system was used for multispectral ex vivo imaging and quantitative evaluation of freshly excised benign and malignant human ovarian tissues. A total of 14 ovaries from 11 patients undergoing oophorectomy were investigated. Using a logistic regression model with seven significant spectral and spatial features extracted from SFDI images, a sensitivity of 94.06% and specificity of 93.53% were achieved for prediction of histologically confirmed invasive carcinoma.
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Colorectal cancer is the second leading cause of cancer death in the United States. Significant limitations in screening and surveillance modalities continue to hamper early detection of primary cancers or recurrences after therapy. In this study, we describe a new registered ultrasound (US) and acoustic-resolution photoacoustic microscopy (AR-PAM) system and report its initial testing in ex vivo human colorectal tissue. A total of 8 colorectal specimens were imaged, which included 2 polyps, 4 malignant colon cancers, and 2 treated colorectal cancers. In each specimen, normal tissue was also imaged for internal control. Initial data have demonstrated the feasibility of identifying colorectal cancer imaging features and the invasion depth using co-registered US and an AR-PAM system. In normal tissue, we found that our system consistently demonstrates the multi-layer structure of normal colonic tissue while differentiating layers with elevated vascularity; these findings highly correlated with histologic findings of each specimen. For malignant colorectal samples, the tissue structure is highly disorganized as seen in US, and photoacoustic imaging revealed distorted vascular distribution inside the tumor. Notably, AR-PAM of tumor beds after complete tumor destruction by radiation and chemotherapy yielded a pattern identical to benign tissue. Quantitative analysis of photoacoustic spectral slope has demonstrated more high-frequency components in malignant tissue as compared to the normal colon tissue, which may be caused by significantly increased microvessel networks. In summary, we demonstrate the successful differentiation of benign and malignant colorectal tissue with our co-registered ultrasound and photoacoustic system.
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In this study, a full field optical coherence tomography (FFOCT) system was used to analyze and classify normal and malignant human ovarian tissue. 14 ovarian tissue samples (7 normal, 7 malignant) were imaged with the FFOCT system and five features were extracted by analyzing the normalized image histogram from 56 FFOCT images, based on the differences in the morphology of the normal and malignant tissue samples. A generalized linear model (GLM) classifier was trained using 36 images, and sensitivity of 95.3% and specificity of 91.1% was obtained. 20 images were used to test the model, and a sensitivity of 91.6% and specificity of 87.7% was obtained.