OBJECTIVE: Hoarseness is primarily perceived as breathiness or roughness. Despite the various tools that quantitatively assess hoarseness, roughness has been difficult to quantify because of its complex acoustic structure, such as subharmonics. The parameter obtained from the two-stage cepstral analysis is promising for evaluating roughness. Thus, this study aimed to improve the accuracy of the parameter using a customized pitch setting and investigate the relationship between roughness and subharmonics.
METHODS: The design is a retrospective study.
METHODS: Two-stage cepstral analysis was used to analyze the voice recordings of 455 participants, speech impaired and normal controls, using the Analysis of Dysphonia in Speech and Voice and Praat software. For validation, the ground truth of subharmonics was visually quantified using a narrowband spectrogram. The reliability and validity of the two-stage cepstral analysis and subharmonics measures on spectrograms were evaluated.
RESULTS: The two-stage cepstral analysis showed a very strong correlation (r = 0.963) between the two software programs. Intra- and inter-rater reliability of the subharmonics measures on spectrograms were also good. Two-stage cepstral analysis showed that even with customized pitch settings, the diagnostic systems and correlations for perceptual roughness and subharmonics were weak to moderate. The subharmonics measures on spectrograms showed a strong correlation with roughness and moderate diagnostic accuracy of subharmonics.
CONCLUSIONS: The two-stage cepstral analysis showed some improvement in diagnostic accuracy and correlation with customized pitch settings, but it did not sufficiently detect subharmonics or roughness. The analysis using subharmonics measures on spectrograms proved the high correlation between subharmonics and roughness, indicating that developing acoustic analysis parameters that sufficiently detect subharmonics is necessary.

As-prepared mesoporous silicon nanoparticles, which were synthesized by electrochemical etching of crystalline silicon wafers followed by high-energy milling in water, were explored as a sonosensitizer in aqueous media under irradiation with low-intensity ultrasound at 0.88 MHz. Due to the mixed oxide-hydride coating of the nanoparticles\' surfaces, they showed both acceptable colloidal stability and sonosensitization of the acoustic cavitation. The latter was directly measured and quantified as a cavitation energy index, i.e., time integral of the magnitude of ultrasound subharmonics. The index turned out to be several times greater for nanoparticle suspensions as compared to pure water, and it depended nonmonotonically on nanoparticle concentration. In vitro tests with Lactobacillus casei revealed a dramatic drop of the bacterial viability and damage of the cells after ultrasonic irradiation with intensity of about 1 W/cm2 in the presence of nanoparticles, which themselves are almost non-toxic at the studied concentrations of about 1 mg/mL. The experimental results prove that nanoparticle-sensitized cavitation bubbles nearby bacteria can cause bacterial lysis and death. The sonosensitizing properties of freshly prepared mesoporous silicon nanoparticles are beneficial for their application in mild antibacterial therapy and treatment of liquid media.

In this paper we study the generation and behavior of subharmonics in a bubbly liquid confined in an acoustic resonator, through numerical simulations carried out at finite-amplitude acoustic pressure. Several configurations in terms of resonator length and driving frequency are considered here. Our results show that these frequency components, created from a higher-frequency signal at the source (ultrasound), are due to the nonlinearity of the medium at high acoustic-pressure amplitude and to the configuration of the resonator (geometry and boundaries). We also show that they have an amplitude-threshold dependence, which is in concordance with the literature. The response of these subharmonics to different sequences of pressure amplitudes also reveals the hysteretic nature of the bubbly liquid.

The pressure threshold for 1/2 order subharmonic (SH) emissions and period doubling during the oscillations of ultrasonically excited bubbles is thought to be minimum when the bubble is sonicated with twice its resonance frequency (fr). This estimate is based on studies that simplified or neglected the effects of thermal damping. In this work, the nonlinear dynamics of ultrasonically excited bubbles is investigated accounting for the thermal dissipation. Results are visualized using bifurcation diagrams as a function of pressure. Here we show that, and depending on the gas, the pressure threshold for 1/2 order SHs can be minimum at a frequency between 0.5fr≤f≤0.6fr. In this frequency range, the generation of 1/2 order SHs are due to the occurrence of 5/2 order ultra-harmonic resonance. The stability of such oscillations is size dependent. For an air bubble immersed in water, only bubbles bigger than 1 μm in diameter are able to emit non-destructive SHs in these frequency ranges.

Subharmonics are an important class of voice signals, relevant for speech, pathological voice, singing, and animal bioacoustics. They arise from special cases of amplitude (AM) or frequency modulation (FM) of the time-domain signal. Surprisingly, to date there is only one open source subharmonics detector available to the scientific community: Sun\'s subharmonic-to-harmonic ratio (SHR). Here, this algorithm was subjected to a formal evaluation with two data sets of synthesized and empirical speech samples. Both data sets consisted of electroglottographic (EGG) signals, ie, a physiological correlate of vocal fold oscillation that bypasses vocal tract acoustics. Data Set I contained 2560 synthesized EGG signals with varying degrees of AM and FM, fundamental frequency (fo), periodicity, and signal-to-noise ratio (SNR). Data Set II was made up of 25 EGG samples extracted from the CMU Arctic speech data base. For a \"ground truth\" of subharmonicity, these samples were manually annotated by a group of five external experts. Analysis of the synthesized data suggested that the SHR metric is relatively robust as long as the subharmonic modulation extent is below 0.35 and 0.7 for the FM and AM scenarios, respectively. In the CMU Arctic speech data samples, the SHR analysis reached a maximum sensitivity of about 87% at a specificity of over 90%, but only for adaptive algorithm parameter settings. In contrast, the algorithm\'s default parameter settings could only successfully classify about 9% of all subharmonic instances. The SHR is a useful metric for assessing the degree of subharmonics contained in voice signals, but only at adaptive parameter settings. In particular, the frequency ceiling should be set to five times the highest fo, and the frame length to at least five times the largest fundamental period of the analyzed signal. For subharmonic classification a threshold of SHR  ≥  0.01 is recommended.

OBJECTIVE: Automatic acoustic measures of voice quality in people with Down syndrome (DS) do not reliably reflect perceived voice qualities. This study used acoustic data and visual spectral data to investigate the relationship between perceived voice qualities and acoustic measures.
METHODS: Participants were four young adults (two males, two females; mean age 23.8 years) with DS and severe learning disabilities, at least one of whom had a hearing impairment.
METHODS: Participants imitated sustained /i/, /u/, and /a/ vowels at predetermined target pitches within their vocal range. Medial portions of vowels were analyzed, using Praat, for fundamental frequency, harmonics-to-noise ratio, jitter, and shimmer. Spectrograms were used to identify the presence and the duration of subharmonics at onset and offset, and mid-vowel. The presence of diplophonia was assessed by auditory evaluation.
RESULTS: Perturbation data were highest for /a/ vowels and lowest for /u/ vowels. Intermittent productions of subharmonics were evident in spectrograms, some of which coincided with perceived diplophonia. The incidence, location, duration, and intensity of subharmonics differed between the four participants.
CONCLUSIONS: Although the acoustic data do not clearly indicate atypical phonation, diplophonia and subharmonics reflect nonmodal phonation. The findings suggest that these may contribute to different perceived voice qualities in the study group and that these qualities may result from intermittent involvement of supraglottal structures. Further research is required to confirm the findings in the wider DS population, and to assess the relationships between voice quality, vowel type, and physiological measures.

OBJECTIVE: In this paper, a nonlinear least squares fitting method was proposed to quantify subharmonic mucosal waves.
METHODS: Subharmonic mucosal waves from 10 excised canine larynges were recorded using digital kymography and analyzed using nonlinear least squares and linear least squares methods. Amplitudes of fundamental and subharmonic mucosal wave components of right-upper, right-lower, left-upper, and left-lower vocal fold lips were calculated. Lastly, phase differences of fundamental and subharmonic components of the left and right vocal folds were compared.
RESULTS: The results showed that the nonlinear least squares analysis method provides a more effective complement to the linear fitting method for subharmonic mucosal wave extraction. There was a significant difference in amplitudes between the subharmonic and the fundamental components of mucosal waves (P < 0.05). The phase differences of the fundamental and the subharmonic components of the right and left vocal folds were not significantly different.
CONCLUSIONS: The application of the nonlinear least squares analysis method in digital kymography is useful for the characterization of subharmonic mucosal waves.

Freddie Mercury was one of the twentieth century\'s best-known singers of commercial contemporary music. This study presents an acoustical analysis of his voice production and singing style, based on perceptual and quantitative analysis of publicly available sound recordings. Analysis of six interviews revealed a median speaking fundamental frequency of 117.3 Hz, which is typically found for a baritone voice. Analysis of voice tracks isolated from full band recordings suggested that the singing voice range was 37 semitones within the pitch range of F#2 (about 92.2 Hz) to G5 (about 784 Hz). Evidence for higher phonations up to a fundamental frequency of 1,347 Hz was not deemed reliable. Analysis of 240 sustained notes from 21 a-cappella recordings revealed a surprisingly high mean fundamental frequency modulation rate (vibrato) of 7.0 Hz, reaching the range of vocal tremor. Quantitative analysis utilizing a newly introduced parameter to assess the regularity of vocal vibrato corroborated its perceptually irregular nature, suggesting that vibrato (ir)regularity is a distinctive feature of the singing voice. Imitation of subharmonic phonation samples by a professional rock singer, documented by endoscopic high-speed video at 4,132 frames per second, revealed a 3:1 frequency locked vibratory pattern of vocal folds and ventricular folds.

Multifrequency atomic force microscopy holds promise as a method to provide qualitative and quantitative information about samples with high spatial resolution. Here, we provide experimental evidence of the excitation of subharmonics in ambient conditions in the regions where capillary interactions are predicted to be the mechanism of excitation. We also experimentally decouple a second mechanism for subharmonic excitation that is highly independent of environmental conditions such as relative humidity. This implies that material properties could be mapped. Subharmonic excitation could lead to experimental determination of surface water affinity in the nanoscale whenever water interactions are the mechanism of excitation.

OBJECTIVE: The objective of this study was to evaluate and compare contrast-enhanced subharmonic and harmonic ultrasound as tools for characterizing solid renal masses and monitoring their response to cryoablation therapy.
METHODS: Sixteen patients undergoing percutaneous ablation of a renal mass provided informed consent to undergo ultrasound examinations the morning before and approximately 4 months after cryoablation. Ultrasound contrast parameters during pretreatment imaging were compared to biopsy results obtained during ablation (n = 13). Posttreatment changes were evaluated by a radiologist and compared to contrast-enhanced magnetic resonance imaging (MRI)/computed tomography (CT) follow-up.
RESULTS: All masses initially showed heterogeneous enhancement with both subharmonic and harmonic ultrasound. Early contrast washout in the mass relative to the cortex was observed in 6 of 9 malignant and 0 of 4 benign lesions in subharmonic mode and 8 of 9 malignant and 1 of 4 benign lesions in harmonic imaging. In cases where the lesion was adequately visualized at follow-up (n = 12), subharmonic and harmonic ultrasound showed accuracies of 83% and 75%, respectively, in predicting treatment outcome. Although harmonic imaging showed less overall error, no significant differences (P > .29) in ablation cavity volumes were observed between MRI/CT and either contrast-imaging mode.
CONCLUSIONS: Subharmonic and harmonic contrast-enhanced ultrasound may be a safe and accurate imaging alternative for characterizing renal masses and evaluating their response to cryoablation therapy. Although subharmonic imaging was more accurate in detecting effective cryoablation, harmonic imaging was superior in quantifying ablation cavity volumes.