Automatic online detection of atrial fibrillation based on symbolic dynamics and Shannon entropy.

BACKGROUND: Atrial fibrillation (AF) is the most common and debilitating abnormalities of the arrhythmias worldwide, with a major impact on morbidity and mortality. The detection of AF becomes crucial in preventing both acute and chronic cardiac rhythm disorders. OBJECTIVE: Our objective is to devise a method for real-time, automated detection of AF episodes in electrocardiograms (ECGs). This method utilizes RR intervals, and it involves several basic operations of nonlinear/linear integer filters, symbolic dynamics and the calculation of Shannon entropy. Using novel recursive algorithms, online analytical processing of this method can be achieved. RESULTS: Four publicly-accessible sets of clinical data (Long-Term AF, MIT-BIH AF, MIT-BIH Arrhythmia, and MIT-BIH Normal Sinus Rhythm Databases) were selected for investigation. The first database is used as a training set; in accordance with the receiver operating characteristic (ROC) curve, the best performance using this method was achieved at the discrimination threshold of 0.353: the sensitivity (Se), specificity (Sp), positive predictive value (PPV) and overall accuracy (ACC) were 96.72%, 95.07%, 96.61% and 96.05%, respectively. The other three databases are used as testing sets. Using the obtained threshold value (i.e., 0.353), for the second set, the obtained parameters were 96.89%, 98.25%, 97.62% and 97.67%, respectively; for the third database, these parameters were 97.33%, 90.78%, 55.29% and 91.46%, respectively; finally, for the fourth set, the Sp was 98.28%. The existing methods were also employed for comparison. CONCLUSIONS: Overall, in contrast to the other available techniques, the test results indicate that the newly developed approach outperforms traditional methods using these databases under assessed various experimental situations, and suggest our technique could be of practical use for clinicians in the future.

Experimental demonstration of reflectarray antennas at terahertz frequencies.

Reflectarrays composed of resonant microstrip gold patches on a dielectric substrate are demonstrated for operation at terahertz frequencies. Based on the relation between the patch size and the reflection phase, a progressive phase distribution is implemented on the patch array to create a reflector able to deflect an incident beam towards a predefined angle off the specular direction. In order to confirm the validity of the design, a set of reflectarrays each with periodically distributed 360 × 360 patch elements are fabricated and measured. The experimental results obtained through terahertz time-domain spectroscopy (THz-TDS) show that up to nearly 80% of the incident amplitude is deflected into the desired direction at an operation frequency close to 1 THz. The radiation patterns of the reflectarray in TM and TE polarizations are also obtained at different frequencies. This work presents an attractive concept for developing components able to efficiently manipulate terahertz radiation for emerging terahertz communications.

Flexible terahertz metamaterials for dual-axis strain sensing.

Utilizing an elastic polymer, we design and experimentally demonstrate a four-fold symmetric flexible metamaterial operating at terahertz frequencies. The fabricated metamaterials exhibit good stretchability and recoverability. Two independent resonances can be observed when the structure is probed with linearly polarized terahertz waves in two orthogonal axes. Applying a stretching force along a main axis causes an observable frequency shift in the corresponding resonance, with minimal effect on the other. This study suggests a possible application of flexible metamaterials for dual-axis strain sensing.

Distinct patterns of biomarker expression for atypical intraductal proliferations in prostate cancer.

High-grade prostatic intraepithelial neoplasia (HGPIN) is a well-characterised precursor lesion in prostate cancer. The term atypical intraductal proliferations (AIP) describes lesions with features that are far too atypical to be considered HGPIN, yet insufficient to be diagnosed as intraductal carcinoma of the prostate (IDCP). Here, a panel of biomarkers was assessed to provide insights into the biological relationship between IDCP, HGPIN, and AIP and their relevance to current clinicopathological recommendations. Tissue samples from 86 patients with prostate cancer were assessed by routine haematoxylin and eosin staining and immunohistochemistry (IHC) with a biomarker panel (Appl1/Sortilin/Syndecan-1) and a PIN4 cocktail (34ßE12+P63/P504S). Appl1 strongly labelled atypical secretory cells, effectively visualising intraductal lesions. Sortilin labelling was moderate-to-strong in > 70% of cases, while Syndecan-1 was moderate-to-strong in micropapillary HGPIN/AIP lesions (83% cases) versus flat/tufting HGPIN (≤ 20% cases). Distinct biomarker labelling patterns for atypical intraductal lesions of the prostate were observed, including early atypical changes (flat/tufting HGPIN) and more advanced atypical changes (micropapillary HGPIN/AIP). Furthermore, the biomarker panel may be used as a tool to overcome the diagnostic uncertainty surrounding AIP by supporting a definitive diagnosis of IDCP for such lesions displaying the same biomarker pattern as cribriform IDCP.

Appl1, Sortilin and Syndecan-1 immunohistochemistry on intraductal carcinoma of the prostate provides evidence of retrograde spread.

The presence of intraductal carcinoma of the prostate (IDCP) correlates with late-stage disease and poor outcomes for patients with prostatic adenocarcinoma, but the accurate and reliable staging of disease severity remains challenging. Immunohistochemistry (IHC) has been utilised to overcome problems in assessing IDCP morphology, but the current markers have only demonstrated limited utility in characterising the complex biology of this lesion. In a retrospective study of a cohort of patients who had been diagnosed with IDCP, we utilised IHC on radical prostatectomy sections with a biomarker panel of Appl1, Sortilin and Syndecan-1, to interpret different architectural patterns and to explore the theory that IDCP occurs from retrograde spread of high-grade invasive prostatic adenocarcinoma. Cribriform IDCP displayed strong Appl1, Sortilin and Syndecan-1 labelling patterns, while solid IDCP architecture had high intensity Appl1 and Syndecan-1 labelling, but minimal Sortilin labelling. Notably, the expression pattern of the biomarker panel in regions of IDCP was similar to that of adjacent invasive prostatic adenocarcinoma, and also comparable to prostate cancer showing perineural and vascular invasion. The Appl1, Sortilin, and Syndecan-1 biomarker panel in IDCP provides evidence for the model of retrograde spread of invasive prostatic carcinoma into ducts/acini, and supports the inclusion of IDCP into the five-tier Gleason grading system.

Low-cost ultra-thin broadband terahertz beam-splitter.

A low-cost terahertz beam-splitter is fabricated using ultra-thin LDPE plastic sheeting coated with a conducting silver layer. The beam splitting ratio is determined as a function of the thickness of the silver layer--thus any required splitting ratio can be printed on demand with a suitable rapid prototyping technology. The low-cost aspect is a consequence of the fact that ultra-thin LDPE sheeting is readily obtainable, known more commonly as domestic plastic wrap or cling wrap. The proposed beam-splitter has numerous advantages over float zone silicon wafers commonly used within the terahertz frequency range. These advantages include low-cost, ease of handling, ultra-thin thickness, and any required beam splitting ratio can be readily fabricated. Furthermore, as the beam-splitter is ultra-thin, it presents low loss and does not suffer from Fabry-Pérot effects. Measurements performed on manufactured prototypes with different splitting ratios demonstrate a good agreement with our theoretical model in both P and S polarizations, exhibiting nearly frequency-independent splitting ratios in the terahertz frequency range.

Comprehensive modeling of THz microscope with a sub-wavelength source.

The sub-wavelength THz emission point on a nonlinear electrooptical crystal, used in broadband THz near-field emission microscopy, is computationally modeled as a radiating aperture of Gaussian intensity profile. This paper comprehensively studies the Gaussian aperture model in the THz near-field regime and validates the findings with dual-axis knife-edge experiments. Based on realistic parameter values, the model allows for THz beam characterisation in the near-field region for potential microscopy applications. An application example is demonstrated by scanning over a cyclic-olefin copolymer sample containing grooves placed sub-wavelengths apart. The nature of THz microscopy in the near-field is highly complex and traditionally based on experiments. The proposed validated numerical model therefore aids in the quantitative understanding of the performance parameters. Whilst in this paper we demonstrate the model on broadband electro-optical THz near-field emission microscopy, the model may apply without a loss of generality to other types of THz near-field focused beam techniques.

In vivo terahertz reflection imaging of human scars during and after the healing process.

We use terahertz imaging to measure four human skin scars in vivo. Clear contrast between the refractive index of the scar and surrounding tissue was observed for all of the scars, despite some being difficult to see with the naked eye. Additionally, we monitored the healing process of a hypertrophic scar. We found that the contrast in the absorption coefficient became less prominent after a few months post-injury, but that the contrast in the refractive index was still significant even months post-injury. Our results demonstrate the capability of terahertz imaging to quantitatively measure subtle changes in skin properties and this may be useful for improving scar treatment and management.

Freeze-thaw hysteresis effects in terahertz imaging of biomedical tissues.

There have recently been several studies published involving terahertz (THz) imaging of frozen biomedical samples. In this paper, we investigate the effects of the freeze-thaw cycle on THz properties of porcine muscle and fat samples. For ordinary freezing, there was a significant change in the THz properties after thawing for muscle tissue but not for fat tissue. However, if snap-freezing was combined with fast-thawing instead of ordinary freezing and ordinary thawing, then the freeze-thaw hysteresis was removed.

Gelatin embedding: a novel way to preserve biological samples for terahertz imaging and spectroscopy.

Sample dehydration has traditionally been a challenging problem in ex vivo terahertz biomedical experiments as water content changes significantly affect the terahertz properties and can diminish important contrast features. In this paper, we propose a novel method to prevent sample dehydration using gelatin embedding. By looking at terahertz image data and calculating the optical properties of the gelatin-embedded sample, we find that our method successfully preserves the sample for at least 35 h, both for imaging and spectroscopy. Our novel preservation method demonstrates for the first time the capability to simultaneously maintain sample structural integrity and prevent dehydration at room temperature. This is particularly relevant for terahertz studies of freshly excised tissues but could be beneficial for other imaging and spectroscopy techniques.