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A method to register THz and visible images of cutaneous burn wounds and to calibrate THz image data is presented. Images of partial and full thickness burn wounds in 9 rats were collected over 435 mins. = 7.25 hours following burn induction. A two-step process was developed to reference the unknown structure of THz imaging contrast to the known structure and the features present in visible images of the injury. This process enabled the demarcation of a wound center for each THz image, independent of THz contrast. Threshold based segmentation enabled the automated identification of air (0% reflectivity), brass (100% reflectivity), and abdomen regions within the registered THz images. Pixel populations, defined by the segmentations, informed unsupervised image calibration and contrast warping for display. The registered images revealed that the largest variation in THz tissue reflectivity occurred superior to the contact region at ~0.13%/min. Conversely the contact region showed demonstrated an ~6.5-fold decrease at ~0.02%/min. Exploration of occlusion effects suggests that window contact may affect the measured edematous response.

* Context.--Large cell transformation (LCT) of indolent Bcell lymphomas, such as follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL), signals a worse prognosis, at which point aggressive chemotherapy is initiated. Although LCT is relatively straightforward to diagnose in lymph nodes, a marrow biopsy is often obtained first given its ease of procedure, low cost, and low morbidity. However, consensus criteria for LCT in bone marrow have not been established. Objective.--To study the accuracy and reproducibility of a trained convolutional neural network in identifying LCT, in light of promising machine learning tools that may introduce greater objectivity to morphologic analysis. Design.--We retrospectively identified patients who had a diagnosis of FL or CLL who had undergone bone marrow biopsy for the clinical question of LCT. We scored morphologic criteria and correlated results with clinical disease progression. In addition, whole slide scans were annotated into patches to train convolutional neural networks to discriminate between small and large tumor cells and to predict the patient's probability of transformation. Results.--Using morphologic examination, the proportion of large lymphoma cells ([greater than or equal to]10% in FL and [greater than or equal to]30% in CLL), chromatin pattern, distinct nucleoli, and proliferation index were significantly correlated with LCT in FL and CLL. Compared to pathologist-derived estimates, machine-generated quantification demonstrated better reproducibility and stronger correlation with final outcome data. Conclusions.--These histologic findings may serve as indications of LCT in bone marrow biopsies. The pathologist--augmented with machine system appeared to be the most predictive, arguing for greater efforts to validate and implement these tools to further enhance physician practice., Large cell transformation (LCT) from indolent B-cell lymphoma to diffuse large B-cell lymphoma (DLBCL) is a life-threatening complication. Patients with preceding indolent B-cell lymphomas, commonly follicular lymphoma (FL) or chronic [...]

Reflection mode Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and dielectric windows used to flatten the imaging field. Herein, we present an optical design for non-contact THz imaging of cornea. A beam scanning methodology performs angular, normal incidence sweeps of a focused beam over the corneal surface while keeping the source, detector, and patient stationary. A quasioptical analysis method is developed to analyze the theoretical resolution and imaging field intensity profile. These results are compared to the electric field distribution computed with a physical optics analysis code. Imaging experiments validate the optical theories behind the design and suggest that quasioptical methods are sufficient for designing of THz corneal imaging systems. Successful imaging operations support the feasibility of non-contact in vivo imaging. We believe that this optical system design will enable the first, clinically relevant, in vivo exploration of CTWC using THz technology.

Terahertz (THz) imaging of corneal tissue water content (CTWC) is a proposed method for early, accurate detection and study of corneal diseases. Despite promising results from ex vivo and in vivo cornea studies, interpretation of the reflectivity data is confounded by the contact between corneal tissue and rigid dielectric window used to flatten the imaging field. This work develops a novel imaging system and image reconstruction methods specifically for nearly spherical targets such as human cornea. A prototype system was constructed using a 650 GHz multiplier source and Schottky diode detector. Resolution and imaging field strength measurement from characterization targets correlate well with those predicted by the quasioptical theory and physical optics analysis. Imaging experiments with corneal phantoms and ex vivo corneas demonstrate the hydration sensitivity of the imaging system and reliable measurement of CTWC. We present successful acquisition of non-contact THz images of in vivo human cornea, and discuss strategies for optimizing the imaging system design for clinical use.

A pulsed terahertz (THz) imaging system and millimeter-wave reflectometer were used to acquire images and point measurements, respectively, of five rabbit cornea in vivo. These imaging results are the first ever produced of in vivo cornea. A modified version of a standard protocol using a gentle stream of air and a Mylar window was employed to slightly dehydrate healthy cornea. The sensor data and companion central corneal thickness (CCT) measurements were acquired every 10-15 min over the course of two hours using ultrasound pachymmetry.. Statistically significant positive correlations were established between CCT measurements and millimeter wave reflectivity. Local shifts in reflectivity contrast were observed in the THz imagery; however, the THz reflectivity did not display a significant correlation with thickness in the region probed by the 100 GHz and CCT measurements. This is explained in part by a thickness sensitivity at least 10× higher in the mm-wave than the THz systems. Stratified media and effective media modeling suggest that the protocol perturbed the thickness and not the corneal tissue water content (CTWC). To further explore possible etalon effects, an additional rabbit was euthanized and millimeter wave measurements were obtained during death induced edema. These observations represent the first time that the uncoupled sensing of CTWC and CCT have been achieved in vivo.

Terahertz (THz) spectral properties of human cornea are explored as a function of central corneal thickness (CCT) and corneal water content, and the clinical utility of THz-based corneal water content sensing is discussed. Three candidate corneal tissue water content (CTWC) perturbations, based on corneal physiology, are investigated that affect the axial water distribution and total thickness. The THz frequency reflectivity properties of the three CTWC perturbations were simulated and explored with varying system center frequency and bandwidths (Q-factors). The modeling showed that at effective optical path lengths on the order of a wavelength the cornea presents a lossy etalon bordered by air at the anterior and the aqueous humor at the posterior. The simulated standing wave peak-to-valley ratio is pronounced at lower frequencies and its effect on acquired data can be modulated by adjusting the bandwidth of the sensing system. These observations are supported with experimental spectroscopic data. The results suggest that a priori knowledge of corneal thickness can be utilized for accurate assessments of corneal tissue water content. The physiologic variation of corneal thickness with respect to the wavelengths spanned by the THz band is extremely limited compared to all other structures in the body making CTWC sensing unique amongst all proposed applications of THz medical imaging.

We have developed a system for evaluating magnetic resonance imaging of prostate cancer, using patient-specific 3D printed molds to facilitate MR-histology correlation. Prior to radical prostatectomy a patient receives a multiparametric MRI, which an expert genitourinary radiologist uses to identify and contour regions suspicious for disease. The same MR series is used to generate a prostate contour, which is the basis for design of a patient-specific mold. The 3D printed mold contains a series of evenly spaced parallel slits, each of which corresponds to a known MRI slice. After surgery, the patient's specimen is enclosed within the mold, and all whole-mount levels are obtained simultaneously through use of a multi-bladed slicing device. The levels are then formalin fixed, processed, and delivered to an expert pathologist, who identifies and grades all lesions within the slides. Finally, the lesion contours are loaded into custom software, which elastically warps them to fit the MR prostate contour. The suspicious regions on MR can then be directly compared to lesions on histology. Furthermore, the false-negative and false-positive regions on MR can be retrospectively examined, with the ultimate goal of developing methods for improving the predictive accuracy of MRI. This work presents the details of our analysis method, following a patient from diagnosis through the MR-histology correlation process. For this patient MRI successfully predicted the presence of cancer, but true lesion volume and extent were underestimated. Most cancer-positive regions missed on MR were observed to have patterns of low T2 signal, suggesting that there is potential to improve sensitivity.

Background: Activating point mutations of the RAS gene (NRAS, HRAS, and KRAS) can be seen in benign and malignant thyroid tumors; among these, NRAS mutations are more commonly seen. This study was conducted to evaluate the thyroid risk of malignancy (ROM) associated with RAS mutations in thyroid fine‐needle aspiration (FNA) at the authors' institution. Methods: The authors searched their electronic database system between January 2015 and May 2021 for thyroid FNA cases with any type of RAS mutation. Molecular alterations were identified with the ThyroSeq Genomic Classifier, ThyGeNEXT (thyroid oncogene panel)/ThyraMIR (miRNA classifier), or ThyroSure gene panel. Results: A total of 127 cases (age, 51 ± 14 years; 100 females and 27 males) were identified, and 72 had histologic follow‐up. The overall ROM associated with RAS mutations (with or without any other molecular alterations) was 29%, whereas the ROM was lower (18%) with RAS mutations only. Isolated NRAS, HRAS, and KRAS mutation–associated ROMs were 15%, 27%, and 14%, respectively. Among these RAS‐mutated cases, the cases with a Bethesda category IV cytologic diagnosis had a higher ROM than the cases with a category III diagnosis (38% vs 17%). Twenty‐one histologically confirmed malignant cases were mostly classified on cytology as category IV lesions (14 of 34; 41%), and the remainder were either category III (6 of 35; 17%) or V lesions (1 of 1; 100%). Conclusions: This study demonstrated that the overall RAS mutation–associated ROM in thyroid FNA was intermediate (29%), and isolated HRAS mutations appeared to have a higher ROM (27%) than NRAS and KRAS mutations (15% and 14%, respectively). A RAS mutation can be seen in benign or malignant thyroid diseases. The risk of malignancy is higher when an RAS mutation is associated with other molecular alterations, especially in Bethesda category IV cases. [ABSTRACT FROM AUTHOR]

Objectives: Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy, and early diagnosis, often aided by fine-needle aspiration (FNA), is key to improving patient prognosis. While the current literature describes some of the cytologic features (CFs) of this entity, a comprehensive examination of the CFs has not yet been performed.Methods: We retrospectively searched our electronic database for ATC cases with available slides between January 2008 and December 2019. Cases were examined for 22 CFs and compared with a control group of differentiated thyroid carcinoma.Results: A total of 18 ATC cases meeting our inclusion criteria were identified. Most cases showed moderate to high cellularity (83%) and epithelioid cytomorphology (83%). Architecture included either predominantly groups/clusters of tumor cells (56%) or single tumor cells (44%). The other CFs were as follows: nuclear enlargement (100%), nuclear crowding (89%), nuclear membrane irregularities (100%), multinucleated tumor cells (33%), and background acute inflammatory cells (50%). Of the CFs examined, statistically significant differences between ATC and the control groups were found in the following: nuclear pleomorphism, coarse/clumped chromatin, macronucleoli, apoptosis, and necrosis.Conclusions: Identification of key CFs in FNA coupled with the clinical history aids in the diagnosis of ATC and helps distinguish it from other mimickers. [ABSTRACT FROM AUTHOR]

Background: This study investigated p16 by immunohistochemistry (IHC) on cellblocks (CBs) and human papillomavirus (HPV) by polymerase chain reaction (PCR) in fine‐needle aspiration (FNA) of head and neck squamous cell carcinoma (HNSCC). Methods: Receiver operating characteristic (ROC) curve analysis was used to assess test performance in CBs compared with p16 IHC in 42 surgical specimens from patients with HNSCC and in correlation with HPV by PCR in cytology specimens. The study assessed HPV by PCR in FNA specimens as a substitute for p16 IHC in surgical specimens. Results: Of 42 cases, 38 CBs showed malignant cells as cohesive clusters of viable cells with or without single tumor cells, whereas 4 specimens were composed exclusively of single tumor cells and degenerated cells. All p16‐negative surgical specimens showed an absence of p16 staining in the corresponding CBs (n = 16). In the p16‐positive surgical cases (n = 26), corresponding CBs with tumor clusters (n = 23) showed heterogeneous p16 expression ranging from 40% to 100%; however, scoring single cells was challenging and unreliable because of cellular degradation. ROC curve inspection showed the optimal threshold to be at least 40% p16 staining in tumor clusters with 100% sensitivity and specificity. In cases with inadequate CBs, HPV by PCR on needle rinse showed 88% sensitivity and 100% specificity for p16 expression in surgical specimens. Conclusions: A cutoff of at least 40% p16 expression in tumor clusters may be appropriate for p16 positivity in cytology CB specimens. A positive HPV finding by PCR on needle rinse can be used as a substitute for p16 expression in surgical specimens. Cytology fine‐needle aspiration specimens with tumor clusters in cellblock sections are reliable in determining p16 status by immunohistochemistry in head and neck squamous cell carcinoma. A cutoff of at least 40% in tumor clusters correlates with positive human papillomavirus in cytology specimens and p16 immunohistochemistry in surgical specimens. [ABSTRACT FROM AUTHOR]