Current Bioinformatics - Volume 6, Issue 3, 2011

Voice research is a scientific area, which becomes more and more interesting not only for medical interested scientists or medical doctors but also for other scientific areas like mathematicians or engineers. Most of the communication disorders are due to a disturbance in voice due to laryngeal diseases. Voice is generated in the larynx by the two oscillating vocal folds. The oscillation range of the vocal folds is between 100 Hz and 300 Hz. They are the sound source and constitute the carrier signal for information being transferred through speech. A healthy voice (the acoustical signal) is generated by symmetric and periodic vocal fold oscillations. It is widely held that vocal fold vibration irregularities lead to an impairment of the acoustical voice signal (i.e. hoarseness). Although, this description sounds like an ordinary and easy to understand procedure, the understanding of basic principles of voice production is rather difficult and needs for highly interdisciplinary research approaches. Aims and scope of the given review article series are as follows. Clinical assessment of laryngeal diseases is performed by direct (i.e. endoscopic laryngeal imaging) or indirect (i.e. acoustic and aerodynamic) assessment techniques. However, detailed quantitative knowledge about interrelations between acoustic signal, dynamics of the voice generator, and applied airflow is still in its infancies. Here, the difficulties are due to the limited space within the larynx. Hence other analysis approaches have been developed yielding entire new insight in the process of voice production. The content of this mini hot topic review will first give an overview on up to date clinical assessment techniques, their abilities as well as their limitations (Ziethe et al.). This review yields the conclusion, that most of the assessment techniques only describe the disease but do not give information on laryngeal interrelations. Revealing interrelations in in vivo human experiments is rather impossible due to the very limited space within the larynx. Consequently, efforts on analysing interrelations based on in vitro human and in vivo/in vitro animal experiments are performed due to their vicinity to human in vivo behaviour (Dollinger et al.). In these experiments, relations between stimulation (e.g. muscle tension, air supply) and effect (e.g. dynamics, signal quality) can be analysed in detail. However, due to the reduced reproducibility of in vitro/in vivo experiments, synthetic models based on experience in in vitro experiments are successfully applied and analysed (Kniesburges et al.). Complementary and to verify findings, sophisticated numerical models like 2D-FEM or 3D-FVM models were developed (Alipour et al.). To bring artificial synthetic and numerical models closer to reality in vitro experiments applying rheometers or bio-ractors have been lately engineered to increase the knowledge on tissue attributes of epithelium and muscle, or to gain more insight into local differences on the vocal fold surface (Goodyer et al.). Most of the voice research is focused on “normal” voice production but not on processes occurring during singing voice. The last review article (Kob et al.) will show that this topic yields entire new challenges and that we are just at the beginning of understanding how singing voice is generated. All the proposed methods have the goal to increase our understanding on voice physiology and production within the larynx. In future, improvements for clinical treatment like conservative therapy, surgery or voice rehabilitation are expected.

Purpose: The purpose of this review is to provide a summary of the uses and limitations of techniques used in clinical voice assessment at leading clinics based on journal publications within the last years. Voice assessment techniques of acoustic analysis, perceptual analysis, vocal fold vibration and of aerodynamic measurements are presented regarding the information they provide and their limitations. Conclusion: Various assessment approaches are conducted to evaluate voice quality and to classify the underlying voice disorder. Recordings of the acoustics and dynamics of the vocal folds describe the disease but do not give any information on the laryngeal interrelations. Vocal functioning including the dependencies between laryngeal structures, acoustics and airflow remains unclear. Investigations of these dependencies require in vitro experiments, synthetic models and numerical analysis to describe exactly all parameters of phonation.

Experiments on human and on animal excised specimens as well as in vivo animal preparations are so far the most realistic approaches to simulate the in vivo process of human phonation. These experiments do not have the disadvantage of limited space within the neck and enable studies of the actual organ necessary for phonation, i.e., the larynx. The studies additionally allow the analysis of flow, vocal fold dynamics, and resulting acoustics in relation to well-defined laryngeal alterations. Purpose of Review: This paper provides an overview of the applications and usefulness of excised (human/animal) specimen and in vivo animal experiments in voice research. These experiments have enabled visualization and analysis of dehydration effects, vocal fold scarring, bifurcation and chaotic vibrations, three-dimensional vibrations, aerodynamic effects, and mucosal wave propagation along the medial surface. Quantitative data will be shown to give an overview of measured laryngeal parameter values. As yet, a full understanding of all existing interactions in voice production has not been achieved, and thus, where possible, we try to indicate areas needing further study. Recent Findings: A further motivation behind this review is to highlight recent findings and technologies related to the study of vocal fold dynamics and its applications. For example, studies of interactions between vocal tract airflow and generation of acoustics have recently shown that airflow superior to the glottis is governed by not only vocal fold dynamics but also by subglottal and supraglottal structures. In addition, promising new methods to investigate kinematics and dynamics have been reported recently, including dynamic optical coherence tomography, X-ray stroboscopy and three-dimensional reconstruction with laser projection systems. Finally, we touch on the relevance of vocal fold dynamics to clinical laryngology and to clinically-oriented research.

The process of human phonation involves a complex interaction between the physical domains of structural dynamics, fluid flow, and acoustic sound production and radiation. Given the high degree of nonlinearity of these processes, even small anatomical or physiological disturbances can significantly affect the voice signal. In the worst cases, patients can lose their voice and hence the normal mode of speech communication. To improve medical therapies and surgical techniques it is very important to understand better the physics of the human phonation process. Due to the limited experimental access to the human larynx, alternative strategies, including artificial vocal folds, have been developed. The following review gives an overview of experimental investigations of artificial vocal folds within the last 30 years. The models are sorted into three groups: static models, externally driven models, and self-oscillating models. The focus is on the different models of the human vocal folds and on the ways in which they have been applied.

Acoustic data has long been harvested in fundamental voice investigations since it is easily obtained using a microphone. However, acoustic signals alone do not reveal much about the complex interplay between sound waves, structural surface waves, mechanical vibrations, and fluid flow involved in phonation. Available high speed imaging techniques have over the past ten years provided a wealth of information about the mechanical deformation of the superior surface of the larynx during phonation. Time-resolved images of the inner structure of the deformable soft tissues are not yet feasible because of low temporal resolution (MRI and ultrasound) and x-ray dose-related hazards (CT and standard xray). One possible approach to circumvent these challenges is to use mathematical models that reproduce observable behavior such as phonation frequency, closed quotient, onset pressure, jitter, shimmer, radiated sound pressure, and airflow. Mathematical models of phonation range in complexity from systems with relatively small degrees of freedom (multi-mass models) to models based on partial differential equations (PDEs) mostly solved by finite element (FE) methods resulting in millions of degrees-of-freedom. We will provide an overview about the current state of mathematical models for the human phonation process, since they have served as valuable tools for providing insight into the basic mechanisms of phonation and may eventually be of sufficient detail and accuracy to allow surgical planning, diagnostics, and rehabilitation evaluations on an individual basis. Furthermore, we will also critically discuss these models w.r.t. the used geometry, boundary conditions, material properties, their verification, and reproducibility.

For understanding the phonatory process in human voice production, physical as well as numerical models have been suggested. Material properties within these models are crucial for achieving vocal fold dynamics being close to in vivo human laryngeal dynamics. Hence, different approaches have been suggested to gain insight into human laryngeal tissue, evaluate clinical treatment, as well as to analyze and verify parameters within synthetically built vocal folds. Purpose of Review: The authors want to give an overview of approaches on receiving material parameters being important in voice research. For the different devices and methods being applied for different set-ups, we will present the functionality and applicability. Hence, for future work, this review shall give an indication, what kind of measurement techniques are suitable for the intended study, advantages or disadvantages of the approaches, and what parameters can be obtained from them. Recent Findings: For in vivo experiments, Color Doppler Imaging was found to be suitable for receiving vocal fold stiffness properties. Applying rheological measurements, the elastic modulus and the dynamic viscosity can be determined. In combination with histological analysis it is possible to objectively evaluate clinical treatment. Optical Coherence Tomography enabled to detect tissue boundaries for in vitro vocal folds. A pipette aspiration setup allowed to identifying spacially resolved mechanical properties of synthetic vocal folds. Numerical biomechanical models like finite element models have shown to be suitable to identify isotropic elastic material parameters

The breadth of expression in singing depends on fine control of physiology and acoustics. In this review, the basic concepts from speech acoustics, including the source-filter model, models of the glottal source and source-filter interactions, are described. The precise control, the extended pitch range, the timbre control and, in some cases, the uses of alternate phonation modes all merit further attention and explanation. Here we review features of the singing voice and the understanding that has been delivered by new measurement techniques. We describe the glottal mechanisms and the control of vocal tract resonances used in singing. We review linear and nonlinear components of the voice and the way in which they are measured and modelled and discuss the aero-acoustic models. We conclude with a list of open questions and active fields of research.

Today, cutting edge research is being conducted at the intersection of the fields of cryptography, steganography and molecular genetics. DNA has emerged as a promising new carrier medium for hidden information and DNA-based watermarks, as a special kind of DNA steganography. DNA-based watermarks are helpful tools to identify the unauthorized use of genetically modified organisms protected by patents. Furthermore, they have been recently applied to distinguish between wildtype and artificially designed genomes. However, these watermarks must not be integrated randomly into the genome of living organisms, due to the fact that they might affect cellular functions. Artificial DNA can, for instance, alter the primary sequence and thus the function of a protein when integrated into such coding regions. To counteract these problems, several groups have developed algorithms that hide information in living organisms without affecting them. These algorithms are mainly based on the degenerative genetic code. Mutations occurring infrequently can be detected and even be corrected by some of the published methods using parity bits or sophisticated mutation correction codes. Nevertheless, the underlying assumptions of the mutation scenarios in all existing DNA watermarking procedures are rather artificial. Mutations are treated as being uniformly distributed, and thus, these methods are not able to capture and reflect the de facto underlying biological principles of mutations, which are very specific and often accumulated. Thus, realistic mutation scenarios have to be developed for establishing practically applicable watermarking procedures for biotechnological applications.

Advancements in methods and tools used in the solving of crystal structures account for the continuously increasing number of compounds available in databases. Various methods and tools are employed in current bioinformatics to screen, retrieve and analyze lead compounds from databases for drug design and industrial use, bringing marked advantages in terms of reducing the time and cost of studies. However, a pivotal point in lead compounds retrieval is the proper understanding and representation of their binding interactions. In this review we compare current methods used in virtual screening and post screening analysis of lead compounds which employ interaction profiles as a key feature. We also emphasize the use of such methods in mining novel compounds for manufacturing nutritional supplements, cosmetics and other industrial products.