The effect of air pockets in the urinary bladder on the temperature distribution during loco-regional hyperthermia treatment of bladder cancer patients.

PURPOSE: Loco-regional hyperthermia combined with mitomycin C is used for treatment of nonmuscle invasive bladder cancer (NMIBC). Air pockets may be present in the bladder during treatment. The aim of this study is to quantify the effect of air pockets on the thermal dose of the bladder. METHODS: We analysed 16 patients treated for NMIBC. Loco-regional hyperthermia was performed with the in-house developed 70 MHz AMC-4 hyperthermia device. We simulated treatments with the clinically applied device settings using Plan2Heat (developed in-house) including the air pockets delineated on CT scans made following treatment, and with the same volume filled with urine. Temperature distributions simulated with and without air pockets were compared. RESULTS: The average air and fluid volumes in the bladder were 6.0 ml (range 0.8 - 19.3 ml) and 183 ml (range 47-322 ml), respectively. The effect of these air pockets varied strongly between patients. Averaged over all patients, the median bladder wall temperature (T50) remained unchanged when an air pocket was present. Temperature changes exceeded ±0.2 °C in, on average, 23% of the bladder wall volume (range 1.3-59%), in 6.0% (range 0.6-20%) changes exceeded ±0.5 °C and in 3.2% (range 0.0-7.4%) changes exceeded ±1.0 °C. There was no correlation between the differences in temperature and the air pocket or bladder volume. There was a positive correlation between air pocket surface and temperature heterogeneity. CONCLUSION: Presence of air causes more heterogeneous bladder wall temperatures and lower T90, particularly for larger air pockets. The size of air pockets must therefore be minimized during bladder hyperthermia treatments.

Predictive value of simulated SAR and temperature for changes in measured temperature after phase-amplitude steering during locoregional hyperthermia treatments.

INTRODUCTION: On-line adaptive hyperthermia treatment planning can be useful to suppress treatment limiting hot spots and improve tumor temperatures during locoregional hyperthermia. This requires adequate prediction of changes in heating patterns after phase-amplitude steering. We investigated the predictive value of simulated SAR and temperature for changes in measured temperature after phase-amplitude steering during locoregional hyperthermia. METHODS: All treatment sessions of 75 patients with pelvic malignancies treated between September 2013 and March 2018 were evaluated. Phase-amplitude adaptations during the 60 min steady-state period were analyzed. Treatment planning was performed using Plan2Heat, based on CT scans with (thermometry) catheters in the vagina, rectum, and bladder in situ. The predicted SAR and temperature along the thermometry tracks were extracted from the simulated distributions. Correlations between changes in average measured temperature and the simulated SAR and temperature were evaluated for single phase-amplitude steering events, unaccompanied by other (steering) actions. RESULTS: A total of 67 phase-amplitude steering events were suitable for analysis. Simulated changes in both SAR and temperature correlated with the measured temperature changes. For the vagina, R2 = 0.44 and R2 = 0.55 for SAR and temperature, respectively. For the rectum, these values were 0.53 for SAR and 0.66 for temperature. Correlations for the bladder were weaker: R2 = 0.15 and R2 = 0.14 for SAR and temperature, respectively. This can be explained by convection in the bladder fluid, unaccounted for by present treatment planning. CONCLUSION: Treatment planning can predict changes in an average temperature after phase-amplitude steering. This allows on-line support with phase-amplitude steering to optimize hyperthermia treatments.

Improving hyperthermia treatment planning for the pelvis by accurate fluid modeling.

PURPOSE: Hyperthermia is an established (neo)adjuvant treatment modality for a number of pelvic malignancies. Optimal treatment of these tumors requires robust treatment planning, but up until now, the urinary bladder was not modeled accurately, making current simulations less reliable. The authors improved the dielectric and thermophysical model of the urinary bladder in their treatment planning system, and showed the improvements using phantom experiments. METHODS: The authors suspended a porcine bladder in muscle tissue equivalent gel and filled it with 120 ml 0.9% saline. The authors heated the phantom during 15 min with their deep hyperthermia device, using clinical settings, and measured the temperature both inside and outside the bladder. The authors simulated the experiment, both using the clinically used treatment planning system, and using the improved model featuring correct dielectric properties for the bladder content and an enhanced thermophysical model, enabling the simulation of convection. RESULTS: Although the dielectric changes have an impact throughout the phantom, the dominant effect is a higher net heat absorption in the bladder. The effects of changing the thermophysical model are limited to the bladder and its surroundings, but result in a very different temperature profile. The temperatures predicted by the simulations using the new bladder model were in much better agreement with the measurements than those predicted by currently used treatment planning system. CONCLUSIONS: Modeling convection in the urinary bladder is very important for accurate hyperthermia treatment planning in the pelvic area.

Generic method for automatic bladder segmentation on cone beam CT using a patient-specific bladder shape model.

PURPOSE: The aim of this study is to develop and validate a generic method for automatic bladder segmentation on cone beam computed tomography (CBCT), independent of gender and treatment position (prone or supine), using only pretreatment imaging data. METHODS: Data of 20 patients, treated for tumors in the pelvic region with the entire bladder visible on CT and CBCT, were divided into four equally sized groups based on gender and treatment position. The full and empty bladder contour, that can be acquired with pretreatment CT imaging, were used to generate a patient-specific bladder shape model. This model was used to guide the segmentation process on CBCT. To obtain the bladder segmentation, the reference bladder contour was deformed iteratively by maximizing the cross-correlation between directional grey value gradients over the reference and CBCT bladder edge. To overcome incorrect segmentations caused by CBCT image artifacts, automatic adaptations were implemented. Moreover, locally incorrect segmentations could be adapted manually. After each adapted segmentation, the bladder shape model was expanded and new shape patterns were calculated for following segmentations. All available CBCTs were used to validate the segmentation algorithm. The bladder segmentations were validated by comparison with the manual delineations and the segmentation performance was quantified using the Dice similarity coefficient (DSC), surface distance error (SDE) and SD of contour-to-contour distances. Also, bladder volumes obtained by manual delineations and segmentations were compared using a Bland-Altman error analysis. RESULTS: The mean DSC, mean SDE, and mean SD of contour-to-contour distances between segmentations and manual delineations were 0.87, 0.27 cm and 0.22 cm (female, prone), 0.85, 0.28 cm and 0.22 cm (female, supine), 0.89, 0.21 cm and 0.17 cm (male, supine) and 0.88, 0.23 cm and 0.17 cm (male, prone), respectively. Manual local adaptations improved the segmentation results significantly (p < 0.01) based on DSC (6.72%) and SD of contour-to-contour distances (0.08 cm) and decreased the 95% confidence intervals of the bladder volume differences. Moreover, expanding the shape model improved the segmentation results significantly (p < 0.01) based on DSC and SD of contour-to-contour distances. CONCLUSIONS: This patient-specific shape model based automatic bladder segmentation method on CBCT is accurate and generic. Our segmentation method only needs two pretreatment imaging data sets as prior knowledge, is independent of patient gender and patient treatment position and has the possibility to manually adapt the segmentation locally.

Comodulation masking release as a function of type of signal, gated or continuous masking, monaural or dichotic presentation of flanking bands, and center frequency.

Thresholds were measured for detecting a signal centered in a narrow-band noise (NBN) masker (on-frequency band, OFB), for the OFB alone, and with two flanking bands (FBs) added to the OFB, one centered above and one below the OFB. The FBs were either correlated with the OFB or were independent and were presented either to the same ear as the signal plus OFB (monaural condition) or to the opposite ear (dichotic condition). The OFB and FBs were either gated with the signal, or were presented continuously. Three signal types were used: a pure tone; an NBN uncorrelated with the OFB; and an NBN correlated with the OFB. The signal was centered at 0.5, 2, or 6 kHz. Comodulation masking release was estimated either as the difference between threshold with the OFB alone and with the OFB plus correlated FBs [CMR(R-C)], or as the difference between thresholds using correlated and uncorrelated FBs [CMR(U-C)]. Although there were marked individual differences, positive CMR(R-C) values were found in all conditions for all three signal types. CMR(U-C) values were often larger than those for CMR(R-C), reflecting the fact that the uncorrelated FBs tended to produce interference effects, especially for the gated maskers, and at 6 kHz. Values of CMR were larger and more consistent across subjects for continuous than for gated maskers. For continuous maskers, the values of CMR tended to be smallest for the correlated-NBN signal. Results are discussed in terms of available cues and in terms of perceptual grouping mechanisms.

Comodulation masking release in subjects with unilateral and bilateral hearing impairment.

Three subjects with unilateral cochlear hearing loss and three subjects with bilateral cochlear hearing loss were tested in three experiments. In the first, their auditory filter shapes were measured for center frequencies of 700 and 2000 Hz, using the notched-noise method. The auditory filters were generally broader for the impaired than for the normal ears. In experiment 2, the threshold for detecting a 2000-Hz signal centered in a band of noise was measured as a function of the noise bandwidth for a Gaussian noise, and for that same noise multiplied (modulated) by a second noise low-pass filtered at 12.5 Hz. For the Gaussian noise, thresholds increased up to a certain noise bandwidth and then flattened off. This bandwidth was usually greater for the impaired than for the normal ears, consistent with the broader auditory filters of the impaired ears. For the modulated noise, thresholds tended to decrease when the noise bandwidth was increased beyond a certain value, indicating comodulation masking release (CMR). The decrease occurred at wider bandwidths for the impaired than for the normal ears. For the unilaterally impaired subjects, the amount of decrease was smaller for the impaired than for the normal ears when tested at equal SPL, but not when tested at equal SL. In experiment 3, the threshold for detecting a 700-Hz signal centered in a 20-Hz-wide band of noise (the on-frequency band, ONB) was measured in the presence of eight flanking bands (FBs) whose envelopes were either identical with that of the ONB (correlated condition) or were uncorrelated. CMR was defined as the difference in threshold between the correlated and uncorrelated conditions. The ONB and the FBs were presented either to the same ear (monaural condition) or to opposite ears (dichotic condition). CMRs tended to be greatest at high levels of the ONB and the FBs. CMRs in the monaural condition were smaller for hearing-impaired than for normal ears. However, at high levels, CMRs in the dichotic condition were similar for normal, bilaterally impaired, and unilaterally impaired subjects. In the latter case, CMRs were similar when the ONB was presented to the normal ear and to the impaired ear of each subject.(ABSTRACT TRUNCATED AT 400 WORDS)

Temporal modulation transfer functions for band-limited noise in subjects with cochlear hearing loss.

The modulation depth required for the detection of sinusoidal amplitude modulation was measured as a function of modulation rate, giving temporal modulation transfer functions (TMTFs). The carrier was a one-octave wide noise centred at 2 kHz, and it was presented in an unmodulated background noise lowpass filtered at 5 kHz. Three subjects with unilateral cochlear hearing loss were tested. For each subject, the normal ear was tested both at the same sound pressure level (SPL) and at the same sensation level (SL) as the impaired ear. The TMTFs were essentially the same for the normal and impaired ears, both at equal SPL and at equal SL. The better ears of three subjects with bilateral cochlear losses were also tested. Again, TMTFs were essentially the same as obtained for normal ears. These results suggest that temporal resolution is not necessarily adversely affected by cochlear hearing loss, at least as measured by this task.

Some factors affecting the magnitude of comodulation masking release.

This paper examines some of the factors that can affect the magnitude of comodulation masking release (CMR). In experiment I, psychometric functions were measured for the detection of a 1-kHz sinusoidal signal in a "multiplied" narrow-band noise centered at 1 kHz (reference condition) and the same noise with two comodulated flanking bands added. The functions were slightly steeper for the comodulated than for the reference masker. Thus CMRs measured at a high percent correct point were slightly (0.4 dB) larger than CMRs measured at a low percent correct point. Large individual differences were found for the reference masker but not for the comodulated masker. Experiment II compared CMRs obtained with narrow-band Gaussian noise and multiplied noise, using a single flanking band. For a flanking band remote from the signal frequency, the CMRs were smaller and more variable for the multiplied noise than for the Gaussian noise. This variability arose mainly from individual differences in the reference condition. Experiment III compared growth-of-masking functions for a signal centered in Gaussian noise and multiplied noise. Thresholds were lower for the multiplied than for the Gaussian noise, and the differences were greatest at high noise levels. The results are consistent with the idea that, for multiplied noise, some subjects can detect a change in the distribution of the envelope of the stimulus, when the signal is added to the masker. Such subjects have low thresholds in the reference condition, and give small CMRs. Other subjects are relatively insensitive to this cue. They have higher thresholds in the reference condition, and give larger CMRs. For Gaussian noise, thresholds for the reference condition are relatively stable across subjects and CMRs tend to be substantial, even for flanking-band frequencies remote from the signal frequency.

Comodulation masking release as a function of bandwidth and time delay between on-frequency and flanking-band maskers.

The threshold for a signal masked by a narrow band of noise centered at the signal frequency (the on-frequency band) may be reduced by adding to the masker a second band of noise (the flanking band) whose envelope is correlated with that of the first band, an effect called comodulation masking release (CMR). This paper examines CMR as a function of masker bandwidth and time delay between the envelopes of the on-frequency and flanking bands. The 1.0-kHz sinusoidal signal had a duration of 400 ms. The on-frequency band was presented alone (reference condition) or with the flanking band. The flanking-band envelope was either correlated or uncorrelated with that of the on-frequency band. Flanking-band center frequencies ranged from 0.25-2.0 kHz. The flanking band was presented either in the same ear as the on-frequency band (monaural condition) or in the opposite ear (dichotic condition). The noise bands had bandwidths of 6.25, 25, or 100 Hz. In the correlated conditions, the flanking-band envelope was delayed with respect to that of the on-frequency band by 0, 5, 10, or 20 ms. For the 100-Hz bandwidth, CMRs were small (typically less than 1 dB) in both monaural and dichotic conditions at all delay times. For the 25-Hz bandwidth, CMRs were about 3.5 dB for the 0-ms delay, and decreased to about 1.5 dB for the 20-ms delay. For the 6.25-Hz bandwidth, CMRs averaged about 5 dB and were almost independent of delay time. The results suggest that the absolute delay time is not the critical variable determining CMR. The magnitude of CMR appears to depend on the correlation between the envelopes of the on-frequency and flanking bands. However, the results do not support a model of CMR that assumes that signal threshold corresponds to a constant change in across-band envelope correlation when the correlation is transformed to Fisher's z.

Across-channel masking and comodulation masking release.

These experiments on across-channel masking (ACM) and comodulation masking release (CMR) were designed to extend the work of Grose and Hall [J. Acoust. Soc. Am. 85, 1276-1284 (1989)] on CMR. They investigated the effect of the temporal position of a brief 700-Hz signal relative to the modulation cycle of a 700-Hz masker 100% sinusoidally amplitude modulated (SAM) at a 10-Hz rate, which was either presented alone (reference masker) or formed part of a masker consisting of the 3rd to 11th harmonics of a 100-Hz fundamental. In the harmonic maskers, each harmonic was either SAM with the same 10-Hz modulator phase (comodulated masker) or with a shift in modulator phase of 90 degrees for each successive harmonic (phase-incoherent masker). When the signal was presented at the dips of the envelope of the 700-Hz component, the comodulated masker gave lower thresholds than the reference masker, while the phase-incoherent masker gave higher thresholds, i.e., a CMR was observed. No CMR was found when the signal was presented at the peaks of the envelope. In experiment 1, we replicated the experiment of Grose and Hall, but with an additional condition in which the 600- and 800-Hz components were removed from the masker, in order to investigate the role of within-channel masking effects. The results were similar to those of Grose and Hall. In experiment 2, the signal was added at the peaks of the envelope of the 700-Hz component, but in antiphase to the carrier of that component and at a level chosen to transform the peaks into dips. No CMR was found. Rather, performance was worse for both the comodulated and phase-incoherent maskers than for the reference masker. This was true even when the flanking components in the maskers were all remote in frequency from 700 Hz. In experiment 3, the masker components were all 50% SAM and the signal was added in antiphase at a dip of the envelope of the 700-Hz component, thus making the dip deeper. Performance was worse for the phase-incoherent than for the reference masker and was worse still for the comodulated masker. The results of all three experiments indicate strong ACM effects. CMR was found only when the signal was placed in the dips of the masker envelope and when it produced an increase in level relative to that in adjacent bands.

Comodulation masking release for various monaural and binaural combinations of the signal, on-frequency, and flanking bands.

The threshold for a signal masked by a narrow band of noise centered at the signal frequency (the on-frequency band) may be reduced by adding to the masker a second band of noise (the flanking band) whose envelope is correlated with that of the first band. This effect is called comodulation masking release (CMR). These experiments examine two questions. (1) How does the CMR vary with the number and ear of presentation of the flanking band(s)? (2) Is it possible to obtain a CMR when a binaural masking level difference (BMLD) is already present, and vice versa? Thresholds were measured for a 400-ms signal in a continuous 25-Hz-wide noise centered at signal frequencies (fs) of 250, 1000, and 4000 Hz. This masker was presented either alone or with one or more continuous flanking bands whose envelopes were either correlated or uncorrelated with that of the on-frequency band; their frequencies ranged from 0.5fs to 1.5fs. CMRs were measured for six conditions in which the signal, the on-frequency band, and the flanking band(s) were presented in various monaural and binaural combinations. When a single flanking band was used, the CMR was typically around 2-3 dB. The CMR increased to 5-6 dB if an additional flanking band was added. The effect of the additional band was similar whether it was in the same ear as the original band or in the opposite ear. At the lowest signal frequency, a large CMR was observed in addition to a BMLD and vice versa. At the highest signal frequency, the extra release from masking was small. The results are interpreted in terms of the cues producing the CMR and the BMLD.

Comodulation masking release (CMR) as a function of masker bandwidth, modulator bandwidth, and signal duration.

These experiments examine how comodulation masking release (CMR) varies with masker bandwidth, modulator bandwidth, and signal duration. In experiment 1, thresholds were measured for a 400-ms, 2000-Hz signal masked by continuous noise varying in bandwidth from 50-3200 Hz in 1-oct steps. In one condition, using random noise maskers, thresholds increased with increasing bandwidth up to 400 Hz and then remained approximately constant. In another set of conditions, the masker was multiplied (amplitude modulated) by a low-pass noise (bandwidth varied from 12.5-400 Hz in 1-oct steps). This produced correlated envelope fluctuations across frequency. Thresholds were generally lower than for random noise maskers with the same bandwidth. For maskers less than one critical band wide, the release from masking was largest (about 5 dB) for maskers with low rates of modulation (12.5-Hz-wide low-pass modulator). It is argued that this release from masking is not a "true" CMR but results from a within-channel cue. For broadband maskers (greater than 400 Hz), the release from masking increased with increasing masker bandwidth and decreasing modulator bandwidth, reaching an asymptote of 12 dB for a masker bandwidth of 800 Hz and a modulator bandwidth of 50 Hz. Most of this release from masking can be attributed to a CMR. In experiment 2, the modulator bandwidth was fixed at 12.5 Hz and the signal duration was varied. For masker bandwidths greater than 400 Hz, the CMR decreased from 12 to 5 dB as the signal duration was decreased from 400 to 25 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure to obtain comodulation masking release with frequency-modulated maskers.

These experiments were intended to determine whether comodulation masking release (CMR) occurs for maskers that are modulated in frequency rather than in amplitude. In experiment I, thresholds for a sinusoidal signal were measured in the presence of two continuous sinusoidal maskers: one was centered at the signal frequency (1.0 kHz), and the other was positioned at flanking frequencies ranging from 0.5 to 2.0 kHz. The two maskers were frequency modulated (FM) by the same low-pass-noise modulator (correlated condition) or by independent noise modulators (uncorrelated condition). Thresholds were the same for the correlated and uncorrelated maskers, i.e., no CMR occurred. This was also true when the flanking band was presented in the ear opposite to that containing the signal and the on-frequency masking band. In experiment II, 25-Hz-wide noise maskers were used. The on-frequency band was sinusoidally frequency modulated, while the off-frequency band either had the same FM or no FM. Thresholds were similar for the two conditions, again indicating that no CMR occurred. The results suggest that, unlike amplitude modulation, correlated FM of the masker in different frequency bands does not give rise to a release from masking.

Comodulation masking release (CMR): effects of signal frequency, flanking-band frequency, masker bandwidth, flanking-band level, and monotic versus dichotic presentation of the flanking band.

In experiment I, thresholds for 400-ms sinusoidal signals were measured in the presence of a continuous 25-Hz-wide noise centered at signal frequencies (fs) ranging from 250 to 8000 Hz in 1-oct steps. The masker was presented either alone or together with a second continuous 25-Hz-wide band of noise (the flanking band) whose envelope was either correlated with that of the on-frequency band or was uncorrelated; its center frequency ranged from 0.5 fs to 1.5 fs. The flanking band was presented either in the same ear (monotic condition) as the signal plus masker or in the opposite ear (dichotic condition). The on-frequency band and the flanking band each had an overall level of 67 dB SPL. The comodulation masking release, CMR (U-C), is defined as the difference between the thresholds for the uncorrelated and correlated conditions. The CMR (U-C) showed two components: a broadly tuned component, occurring at all signal frequencies and all flanking-band frequencies, and occurring for both monotic and dichotic conditions; and a component restricted to the monotic condition and to flanking-band frequencies close to fs. This sharply tuned component was small for low signal frequencies, increased markedly at 2000 and 4000 Hz, and decreased at 8000 Hz. Experiment II showed that the sharply tuned component of the CMR (U-C) was slightly reduced in magnitude when the level of the flanking band was 10 dB above that of the on-frequency band and was markedly reduced when the level was 10 dB below, whereas the broadly tuned component and the dichotic CMR (U-C) were only slightly affected. Experiment III showed that the sharply tuned component of the CMR (U-C) was markedly reduced when the bandwidths of the on-frequency and flanking bands were increased to 100 Hz, while the broadly tuned component and the dichotic CMR (U-C) decreased only slightly. The argument here is that the sharply tuned component of the monotic CMR (U-C) results from beating between the "carrier" frequencies of the two masker bands. This introduces periodic zeros in the masker envelope, which facilitate signal detection. The broadly tuned component, which is probably a "true" CMR, was only about 3 dB.