A Modeling Study of Notch Noise Responses of Type III Units in the Gerbil Dorsal Cochlear Nucleus

A computational model of the neural circuitry of the gerbil dorsal cochlear nucleus (DCN), based on the MacGregor’s neuromime model, was used to simulate type III unit (P-cell) responses to notch noise stimuli. The DCN patch model is based on a previous computational model of the cat DCN [Hancock, K. E., and H. F. Voigt. Ann. Biomed. Eng. 27:73–87, 1999]. According to the experimental study of Parsons et al. [Ann. Biomed. Eng. 29:887–896, 2001], the responses of gerbil DCN type III units to notch noise stimuli are similar to those of cat DCN type IV units, which are thought to be spectral notch detectors. This suggests that type III units in the gerbil DCN may serve as spectral notch detectors. In this modeling study, a simplified notch noise response plot—spike discharge rate vs. notch cutoff frequency plot—was used to compare model responses to the experimental results. Parameter estimation and sensitivity analysis of three connection parameters within the DCN patch have been studied and shows the model is robust, providing reasonable fits to the experimental data from 14 of 15 type III units examined [work supported by a grant from NIDCD, Boston University’s Biomedical Engineering department and Hearing Research Center].
INTRODUCTION
The cochlear nucleus (CN) is the sole target of auditory nerve fibers and is the first brainstem nucleus in the ascending auditory pathway. The dorsal part of the cochlear nucleus (DCN) is one of its three sub-nuclei and has initial integration functions. The DCN’s role in audition appears, in part, to be involved in sound localization in the median plane equidistant from the two ears where the traditional sound source location cues, interaural time and level differences, are absent. For broadband signals, the pinna attenuates energy in a narrow band whose center frequency can be correlated with sound source elevation. The pinnae-induced attenuation is called a spectral notch. These notches are seen in the head-related transfer functions (HRTFs), which are the Fourier transforms of the impulse responses from free space sound sources to the tympanic membrane. These spectral features are found in human, cat and gerbil HRTFs.12,13 Principal cells of the DCN, type III units in the gerbil15 and type IV units in the cat,22 exhibit sharp sensitivity to notch noise signals.14,18 This suggests that the DCN is a spectral notch detector across different species.
The previous study of Hancock and Voigt6 used a computational model of the DCN to model the responses of three type IV units to notch noises and presented close fits to the physiological data recorded by Spirou and Young.18 The gerbil DCN has fewer type IV units than the cat DCN (11% type IV units in gerbil vs. 31% in cat)2,17 and is comprised primarily of type III units (62%).2 As the principal units in gerbil DCN, type III units undoubtedly play an important role in gerbil sound localization. In this study, we used the same computational model to fit the physiological data obtained from the gerbil DCN by Parsons et al.15 Despite the fact that type III units have quite different responses to tones than type IV units, this study shows that by modifying the connectivities within the neuron groups we can simulate both type III and type IV units as notch detectors. Also in this work we have good fits for 14 out of 15 type III units in gerbil; this is substantially more modeling data than previously presented and points to the robustness of the DCN model.
RESPONSE MAP SCHEME AND RATE VS. CUTOFF FREQUENCY PLOTS
A response map (RM) is a plot of excitatory and inhibitory responses to tonal stimuli shown in a stimulus frequency vs. sound pressure level plane. It is a popular method to categorize the neurons in the CN of unanethetized, decerebrate animals.4,17,22,23 Type III units are characterized by their RMs (Fig. 1A), which show a center V-shape excitation region flanked by side-band inhibition. The tip of the excitation region points to the unit’s best frequency (BF), the frequency to which the unit was most sensitive. In Fig. 1A, there are seven discharge-rate vs. frequency curves shown for seven sound pressure levels presented. RMs of type IV units typically show an excitatory region over BF and an inhibitory area above that ranging over a broad frequency range; sometimes a narrow excitatory area appears off BF (see Fig. 1 of Ref. 6).FIGURE 1.Physiology of a type III unit: (A) Response map composed of rate vs. frequency curves of unit L021199 1.01 in Parsons et al.15. Excitatory responses are shaded black while inhibitory responses left blank. (B) Rate-level curves when given wideband noise and notch noise stimuli. Only four notch noise responses with notch (nw) widths 1.0 kHz, 2.0 kHz, 4.0 kHz, and 8.0 kHz are shown. (C) Rate vs. Cutoff frequency plot. Here notch widths varies systematically from 0.5 to 8.0 kHz in step of 0.5 kHz. The average rates are calculated from the range of 46–54 dB SPL as shown by black bar in (B).
Responses to broadband noise, in addition to tones, are used to classify units in the DCN. We also used the same notch noise (NN) stimuli in the model simulations as in the physiological experiments.15 These have band reject notches of 30 dB centered at the BF with varying widths. In Fig. 1B, discharge-rate vs. level curves are plotted for broadband noise and four NN stimuli with widths of 1, 2, 4, and 8 kHz. These responses were taken from a series of responses to BF-centered NN stimuli whose widths systematically varied from 0.5 to 8.5 kHz with a 0.5 kHz step. For Unit L021199 1.01 in Fig. 1 there were 16 NN stimuli applied with widths from 0.5 to 8.0 kHz. Only four NN responses are plotted for clarity.
To summarize the information in these rate-level curves, Spirou and Young18 further characterized NN responses with rate vs. cutoff frequency plots (Fig. 1C), where the firing rates to each NN were averaged over a range of sound levels from 46 to 54 dB SPL, where the inhibition reached the maximum, as indicated with black bar on the abscissa in Fig. 1B. The cutoff frequencies included both the notch noise’s lowpass and the highpass cutoff frequencies, thus the average rate of each notch noise response is plotted twice. In such plots, 11 of 15 units in Parsons et al.'s experimental data showed a specific “Mexican Hat” shape, indicating that when increasing the notch width, the average response rate dropped sharply from excitatory to inhibitory and then showed some degree of recovery. The unit in the figure was excited by the broad-band noise and NN with narrow-notch width (0.5 kHz, not shown in Fig. 1B but shown in Fig. 1C), but was inhibited by NN with wider widths (from 1.0 to 6.0 kHz, also shown in Fig. 1C). Also it showed some degree of recovery to a less inhibitory stage when NN with an even wider notch was applied (from 6.5 to 8.0 kHz, shown in Fig. 1C). This recovery was seen in 11 of 15 units in the paper of Parsons et al.15 Similar responses to NN have been found in type IV units in cat by Spirou and Young.18
This demonstrated the sensitivity of type III units in gerbils to the NNs. Thus, type III units in gerbils are capable of detecting spectral notches as do type IV units in cats.
FIGURE 2.Conceptual model of gerbil dorsal cochlear nucleus circuitry. Only inhibitory connections are shown. The size of the triangles indicates connection strength. The horizontal axis represents the input from the auditory nerve fibers with increasing frequency, which target all cells. Modified from Davis et al.2
CONCEPTUAL MODEL OF DCN CIRCUITRY
To illustrate the functional role of type III units in the gerbil DCN, the conceptual model from Davis et al.2 was chosen (see Fig. 2). The gerbil DCN conceptual model is more complex than the cat model since the principal cells in gerbils can be either type III units or type IV units, including subtypes of type IV units: type IV-i and type IV-T units. In addition, besides type II units and the wide band inhibitor (WBI) units, type III-i units were included in the circuitry to provide necessary inhibitory input to type IV-i units. In this paper, however, we only discuss the properties and responses of type III units, thus only type II units and WBI units are taken as inhibitors.
Auditory nerve (AN) fibers provide excitatory inputs to type II units, type III units and WBI units. However, DCN units show spontaneous activity even after destruction of the cochlea.9 Thus non-specific afferents (NSA) were added to the principal cells in our computational model to provide noncochlear inputs to the DCN (Fig. 3). In order not to confuse physiologically defined unit types and model unit types, we use different names to distinguish them (see Table 1).FIGURE 3.A patch of DCN model. Five cell populations are organized in a tonotopic manner with frequency step equal to 0.005 octaves. The excitatory and inhibitory connections are shown in a single frequency slice. P cells, representing type III units in gerbil and type IV units in cat; I2 cells, type II units; W cells, providing wide band inhibition; AN fibers, the auditory nerve fiber input. Modified From Hancock and Voigt, 1999.6
Fusiform cells in gerbil DCN are mostly type III units in intracellular recording and marking experiments by Hancock and Voigt7 whereas type II units arise from vertical cells in the DCN21 and WBI units are thought to project from the posteroventral CN.20 In addition, WBI units send inhibitory connections to both type IV units (principal units in cat) and type II units in cat DCN. We are assuming that these connections to the gerbil principal units remain intact.TABLE 1.Physiological unit types with corresponding model unit types.Physiological unit typeModel unit typeType III unitsP-cellsType II unitsI2-cellsWideband inhibitorsW-cellsAuditory nerve fibersAN-fibers
METHODS
Organization of the DCN Model
The gerbil model is based on a previous computational model of the cat DCN6 (see Fig. 3). The model contains five cell groups that are arranged into 800 isofrequency slices centered at 5 kHz with two octaves below and above in intervals of 0.005 octaves. Figure 3 shows the connections among the model cells within a single frequency slice, where P-cells represent the principal cells, I2-cells represent interneuron inhibitors with type II responses and W-cells represent wide band inhibitors. AN-fibers excite P-cells, I2-cells and W-cells. W-cells inhibit P-cells and I2-cells. I2-cells inhibit P-cells. P-cells also are excited by non-specific afferents.
The relationship among the model cells can be discussed in terms of the connection parameters as shown in Fig. 4. For a given population of model cells (e.g., P-cells), the target cell “B” will receive N inputs from the “A” source cells, which are chosen from a band of “A” source cells with bandwidth BW, offset from the BF of B by C. The subscript  indicates the source unit, A to the target unit, B. In the simulations shown here, all the P-cells’ BFs will be 5 kHz.FIGURE 4.Group connection parameters. B is the target cell and a group of source cells A connect to it.  and  are the step increase and time constant in response to the input spikes. Here B cell receives N inputs from A cells, which are randomly chosen from a band of bandwidth and center frequency offset specified cells.TABLE 2.Intrinsic parameters.Populationτm (ms)θ (mV)bkτk (ms)Ek (mV)Eex (mV)Ein (mV)W-cells5.04.02.001.0−10+70−10I2-cells6.014.51.751.0−10+70−10P-cells10.07.52.001.0−10+70−10
Neuron Model
The neuron model (Fig. 5) is based on the MacGregor neuromime model,10 which is a parallel circuit model containing the membrane capacitance, leakage conductance, a potassium channel branch and the excitatory/inhibitory connection branches. Each excitatory or inhibitory input will add a branch, with the variable conductance controlled by the parameters, step σ and time constant τ.FIGURE 5.(A) Vm is the membrane potential relative to rest; Cm is membrane capacitance; G is resting conductance; Gk and Ek are variable conductance and reversal potential of potassium; Gex/in and Eex/in are excitatory/inhibitory synaptic conductance and reversal potential. (B) Expression of connection synapse conductance. Target cell will undergo a step increase and exponential decay, time constant in response to input spikes.
Event time is recorded when the membrane potential exceeds its threshold, θ, and the potassium conductance is activated to induce the cell’s refractory period. Thus, the computation is reduced by leaving out the details of action potential generation. The following equations describe the neuronmime model:
where gk = Gk/G, gex = Gex/G, and gin = Gin/G; G, Gk, Gex, and Gin represent respectively the conductances of neuron membrane, potassium channel, excitatory synaptic inputs and inhibitory synaptic inputs. The latter three are normalized by G to simplify the equations. Vm is the membrane potential. Ek, Eex, and Ein represent the reversal potentials. τm and τk are the membrane time constant and the refractory time constant. Equation (1) states the current fluxes across the neuronal membrane. Equation (2) states the change of the potassium conductance, where bk represents the sensitivity to potassium conductance. S is the spiking variable with two alternative values: 1 indicates a cell is firing.TABLE 3.Connection parameters.Connection  (octave) (octave) (ms)0.0Varies1400.06100.00.4480.55100.00.448Varies100.00.1151.40100/0.20.115Varies10−0.2/00.6210.11n/an/a150.153
For target cell B, the variable conductance that represents synapses from source cells A is described by
where SA are the input spikes.
Parameter Values
In the model, we used four intrinsic (τm, θ, bk, and τk) and five connection parameters (, , , , and ). The intrinsic parameter set describes the membrane properties of the cell, which determines the steady firing rate and the threshold sound pressure level of the single cell. The connection parameter set describes the connections between two groups of cells; this is used to specify the connectivity within the neuronal circuitry of the model. We used the intrinsic values in the former work of Hancock and Voigt6 (Table 2), as they have little or no effect on the spectral response characteristics.
FIGURE 6.Best fit of Unit L041499 13.01 and parameter sensitivity analysis. (A) Best fit of the model to physiological data. The best frequency of physiological data and the center frequency of the model data have been lined up through simply translation of the physiological data rate vs. cutoff frequency plot. The circles represents the physiological data and the solid line represents the best fit of the model. The dashed line represents the average spontaneous rate of the physiological data. The minimum error Фmin and the values of the three important parameters of the best fit are shown in the upper left. (B)–(D) Contours of equal Ф/Фmin (1.5, 2, 5, 10, and 15, from inside to outside) showing the sensitivity of the fit to the parameter values. , , and  are held to be the value in the best fit corresponsively in plots (B), (C), and (D).FIGURE 7.Best fit of Unit L110199 2.01 and parameter analysis. Organized as in Fig. 6 except that in the contours plots (B–D) equal Φ/Φmin of 1.1 was added to show the center.FIGURE 8.Best fit of Unit L122299 4.01 and parameter analysis. Organized as in Fig. 6.
MacGregor11 pointed out that the steady state effect of one population on its target is proportional only to the product , which enabled us to set only one parameter from these three to be a free parameter; here we chose , the strength from cell A to B. Thus, only three connection parameters, , , and  were taken into account in the simulations. The values of the parameters are listed in Table 3.
As in Table 3, three parameters were set to be main parameters that vary: , , and . Center offset  and  were set to two possible values 0/−0.2 octaves and 0/0.2 octaves respectively according to the physiological data in cross-correlation studies.  was set to 0.1 to obtain type III RM properties. Non-specific afferent firing rate was set to 80, 90, or 120 spikes/s according to the various spontaneous rates of type III units.
Auditory Nerve Model
AN-fibers were based on the model described by Carney.1 The input to the AN-fiber is a sound pressure signal and the output is a spike train. Each fiber consists of a gammatone filter that provides the frequency selectivity, a nonlinear process that generates an inner hair cell potential and a compartmental model of neurotransmitter release. This in turn creates an instantaneous firing probability. AN-fiber thresholds and spontaneous activity rates were randomly assigned from physiological distributions of these parameters.5
In order to save time, all stimuli were processed by the auditory nerve filter bank once and the spike time responses were saved for use in subsequent simulations of the DCN circuitry.
Simulation Protocol and Data Analysis
All simulations were carried out on an IBM pSeries 655, which is a 48-processor system composed of six nodes. Each p655 node consists of eight Power4 processors running at 1.1 GHz and sharing 16 GB of memory. There are three levels of cache on this machine. Each processor has a 32 KB L1 cache and then each pair of processors share a 1.41 MB L2 cache, and each p655 node shares a 128 MB L3 cache.
To create RMs, the model was stimulated by 50-ms tone bursts presented every 250 ms with a 32-ms delay while sound pressure levels varied from 0 to 60 dB SPL in 2 dB SPL steps and the frequency varied in 0.1 octave steps within a three octave band above and below 5 kHz. Thus, there are 31 frequency slices in one RM simulation. The spikes of the last 40 ms of each trial were used to compute the spontaneous rate and the spikes of the last 40 ms of each tone burst were used to compute the driven rate. In this paper, RMs composed of rate vs. frequency curves for seven levels were plotted (0–60 dB SPL in 10 dB SPL steps). This is because the physiological data were taken only to 60 dB SPL due to increasing recording artifacts above these levels. At each level, the horizontal line represents the unit’s spontaneous discharge rate; excitation and inhibition are shown as rates above and below this line, respectively. The excitatory region was filled black and the inhibitory region left blank.
We used the same notch noises and broadband noise stimuli to obtain rate-level data as in Hancock and Voigt.6 In the simulation the sound level was varied from 0 to 90 dB SPL in 2 dB SPL steps and the noise bursts were presented for 200 ms in 1000-ms trials.
To obtain rate vs. notch cutoff frequency plots, the firing rates from 46 to 54 dB SPL were averaged to capture the most inhibitory area, consistent with Hancock and Voigt.6 These plots are sometimes referred to as “Mexican Hats.”
TABLE 4.Data fits for all 15 type III units.In RefUnitBFSRΦminNSA1Fig. 3AL122299 3.014.3383.490003.25a0.250.902Fig. 3BL021199 1.014.7773.81200.203.25a0.451.803Fig. 3CL110199 2.012.6132.480003.000.120.254Fig. 4AL111799 9.014.992.8800.2−0.22.000.120.255Fig. 4BL122299 4.0111.0144.7800−0.21.250.240.906Fig. 4CL110199 11.024.21211.080001.00a0.150.05a7Fig. 4DL102599 7.0110.2265.190001.500.250.708Fig. 4EL041499 16.013.8308.1800.2−0.22.500.120.209Fig. 4FL021199 4.017.1152.880003.25a0.180.2510Fig. 4GL102599 8.016.4225.680001.500.120.4011Fig. 4HL041499 13.011.2352.480001.250.240.8012Fig. 4IL041499 1.021.399.8800.203.25a0.060.1513Fig. 4JL041499 1.011.2495.8800−0.21.00a0.240.9014Fig. 4KL040700 3.0111.4201.3800.203.000.240.2515Fig. 4LL040700 7.0115.1240.4120002.750.452.00aNote. Ref. refers to Parsons et al.15; BF in kHz, SR in spikes/s, NSA in spikes/s.aThe parameter value reached the parameter limit.
RESULTS
Fit of the Model to Physiological Data and Parameter Sensitivity Analysis
Discharge rate versus cutoff frequency plots were used to evaluate the effectiveness of our DCN model quantitatively when fit to the physiological data obtained by Parsons et al.15 The physiological discharge rate versus cutoff frequency plots were translated along the frequency axis to align the BF of the unit to that of the model at 5 kHz without shape change in logarithmic frequency plots. This operation was done mathematically by scaling the cutoff frequencies by CF/BF, where CF is the center frequency of model and BF is the best frequency of physiological data. This operation also made the after-translation physiological data look like that obtained by notch noise stimuli centered at 5 kHz while notch widths scaled by the factor CF/BF. Then linear interpolation was used to obtain “new” physiological data corresponding to model data cutoff frequencies and this made comparison of fits among different units possible. Here we used an objective function, Φ, to demonstrate quantitatively the fit of one unit, or for comparisons across the units as done by Hancock and Voigt6:
where yd and ym are the mean firing rates in the physiological data and model results respectively, and N is the total number of cutoff frequencies used in the comparison. The value of the objective function is scaled by 500 to make it more readable, consistent with Hancock and Voigt.6
The three parameters , , and , were systematically varied to get the “best fit” (minimum Φ, Φmin) and also to show contours of equal goodness or quality of fit. Center offsets  and , were set to 0 or −0.2 octaves and 0 or 0.2 octaves respectively, and the fitting results were only slightly different with similar Φmin when best fits were obtained. Non-specific afferent (NSA) firing rate was set to 80, 90, or 120 spikes/s to adjust to the various spontaneous rates of type III units and this improved the fits, especially for some low-spontaneous rate units. An alternative way to adjust spontaneous rate was to vary the connection strength of NSA to P-cells as in Hancock and Voigt.6 These two methods show no difference from each other since P-cells are the only targets of the NSA and the different firing rates of NSA or the strength of the connection between NSA and P-cells will only affect the total NSA excitatory inputs to P-cells.
Figures 6–8A show the best fits to three physiological units labeled Unit L041499 13.01, Unit L110199 2.01 and Unit L122299 4.01. Figures 6–8B–D are contours showing parameter sensitivity analyses of these parameters. As shown in the figures,  varied from 1.0 to 3.25 octaves in steps of 0.25 octaves;  varied from 0.05 to 0.5 or from 0.03 to 0.3; and  varied from 0.1 to 1.0 or from 0.05 to 0.5
Very good fits are obtained for these three units. Not only are the values of Φmin small, but the centers of the contours are shown clearly and the contours themselves resemble ellipses.FIGURE 9.Response maps and rate-level plots for notch noise stimuli. (A, B) Response map composed of rate vs. frequency curves plot of Unit L041499 13.01 and the model using the set of best fit parameters in Fig. 6. The best frequency of this unit is 1.2 kHz and has been moved to 5 kHz with the same method in “Mexican Hat” plots for easier comparison to model RM. (C, D) Rate-level curves of broad-band noise and notch noise responses of the unit and the model data.FIGURE 10.Response maps and rate-level plots responding to notch noise stimuli. Unit L110199 2.01. The best frequency of this unit is 2.6 kHz. Picture is organized as in Fig. 9.
Table 4 shows the results for all 15 units. Of the 15 units from Parsons et al., 15 eight units had best fits within closed ellipses. Another six units also gave good fits, although the  parameter in these cases was actually at its limit (four reaching the upper limit and one reaching the lower limit of the parameter range, one reaching the upper limit of ). These 14 units had values of Φmin < 9.8, which shows that the model is robust. The final unit was difficult to fit because the rate vs. notch noise cutoff frequency plot showed additional features (see Parsons et al., Fig. 4C).15
Comparisons Between Physiological Data and Model Data: Response Maps and Notch Noise Rate-Level Curves
Since the rate vs. notch noise cutoff frequency curves are the functions that were modeled, to what extent do the model RMs and notch noise rate-level curves resemble their physiological counterparts? Figures 9–11A and B show the physiological RMs together with the model RMs for the units of Figures 6–8. The model RMs were simulated using the model parameters set found when Φ = Φmin. For two sets of RMs we found that the model RMs show insufficient excitatory regions across the frequency axis when high-level tone bursts are given. This occurs in another five units where the physiological data show wide excitatory regions and indicates that our model parameters may need adjustment to get better tone responses for these units. All three model RMs, however, show nice center excitatory regions and sideband inhibitory regions, which is characteristic of type III units.
Figures 9–11C and D show the rate-level curves corresponding to the BBN and NN stimuli. For Unit L041499 13.01 and Unit L110199 2.01 (Figures 9 and 10), the maximum notch widths could not reach 8.0 kHz since the units had low BFs (1.2 and 2.6 kHz). Unit L122299 4.01 has a higher BF at 11.0 kHz and the notch width was varied from 0.5 to 8.5 kHz as in Parsons et al.15 In general, the responses to BBN are greatest in both model and physiological data, but there are great differences in shape, maximum rate, saturation rates and thresholds. The model’s curves for the NN stimuli are qualitatively similar to the physiology, but again several differences are observed. The model seems to be providing more inhibition than that found in the physiology.
DISCUSSION
Spirou and Young18 showed that type IV units in the cat DCN (projection neurons) are notch detectors. Hancock and Voigt6 used a computational model of cat DCN circuitry, whose P-cells had type IV response properties to show that these also have notch noise sensitivity and that the variability seen in the units’ responses to notch noise are accounted for by parameter variations rather than different circuit arrangements. The gerbil DCN shows far fewer type IV units than the cat and the projection neurons in gerbil DCN are predominately type III units. Parsons et al.15 showed that gerbil type III units are sensitive to notch noises in much the same way as cat DCN type IV units. Thus, it appears that DCN projection neurons from both species are doing the same analysis on notch noise and thus may play similar roles in sound source detection in the median plane.
This study demonstrates that the same computational model used to model the notch noise behavior in cat type IV units can be used to model type III unit notch noise sensitivity in gerbil DCN. The fact that we can use the same neural circuit to model the DCN in both species suggests that perhaps this aspect of the DCN neural circuit is invariant across species.
The Parsons et al.15 data set of 15 type III units provided a rich database to test our model. In all, the model provided reasonable fits to 14 type III units. Prior to this, notch noise responses from only three type IV units from cat were available for modeling.6,18 The objective function used here is the same one used in Hancock and Voigt6; this allowed direct comparisons to that study. In this study, the RMs of the model P-cells with the best-fit parameters were compared to the physiological units’ RMs. The model RMs had excitatory center regions with inhibitory surrounds. These are similar to the physiological RMs and correspond to type III units. The model rate-level curves to broadband noise were similar to the physiological data, but the rate-level curves to notch noise showed many differences. Of course, these data are not part of the objective function used and so we would expect differences. It is possible to modify the objective function to include the rate-level curves, the RMs, or both, and this may be done in the future.FIGURE 11.Response maps and rate-level plots responding to notch noise stimuli. Unit L122299 4.01. The best frequency of this unit is 11.0 kHz. Picture is organized as in Fig. 9.
Our model also shows reduced sensitivity to  in half of the units. Four units reached the upper limit of  octave and two units reached the lower limit of  octave, which indicates that better fits might be obtained by extending the range of . This is not possible in the present version of the model, which is limited to a four octave frequency range.
Non-specific afferent (NSA) firing rate affected the Φmin in a significant way for some units. This was not true, however, for most of the units, where NSA firing rates of 80, 90, and 120 spikes/s produced similar Φmin. The best-fit parameter values and sensitivity plots, however, would change significantly when different rates applied. In general, the parameters of the best fits showed no specific relations to unit BF or spontaneous rates.
The DCN computational models for cat and gerbil are identical in form and differ only in connectivity. The model is still incomplete, however, in that it lacks model cartwheel cells, granule cells and other cell types known to exist. The CN also receives input from somatosensory neurons that subserve tactile and kinesthetic sensations from the trigeminal ganglion16 the interpolar and caudal spinal trigeminal ganglion,8,25 cuneate nucleus19 as well as from other locations. These indicate that in addition to auditory function, the CN is involved in sensory integration at a very early stage in the brain. These are not currently in the model, but provide rich directions to explore in the future.

parameter estimation
sensitivity analysis
hearing
sound localization


Multidetector row CT for imaging the paediatric tracheobronchial tree

The introduction of multidetector row computed tomography (MDCT) scanners has altered the approach to imaging the paediatric thorax. In an environment where the rapid acquisition of CT data allows general hospitals to image children instead of referring them to specialist paediatric centres, it is vital that general radiologists have access to protocols appropriate for paediatric applications. Thus a dramatic reduction in the delivered radiation dose is ensured with optimal contrast bolus delivery and timing, and inappropriate repetition of the scans is avoided. This article focuses on the main principles of volumetric CT imaging that apply generically to all MDCT scanners. We describe the reconstruction techniques for imaging the paediatric thorax and the low-dose protocols used in our institution on a 16-slice detector CT scanner. Examples of the commonest clinical applications are also given.
Introduction
Imaging of the airways with subsequent 2-D and 3-D reconstructions has significantly improved with the advent of the multidetector row computed tomography (MDCT) scanners. These scanners allow volumetric acquisition of isotropic datasets. As a result, the scanning time is significantly reduced, and large anatomical regions are covered within seconds with optimal intravenous contrast material enhancement. MDCT scanners have significantly improved the image quality as the artefacts resulting from partial volume averaging and motion have been dramatically reduced. Additionally, their fast and user-friendly workstations allow postprocessing of impressive multiplanar 2-D and 3-D reconstructions, which are desirable to clinicians as they can be used for comprehensive presurgical planning [1, 2]. In chest applications, the whole of the tracheobronchial tree can be adequately depicted with a single-breath-hold volume acquisition within 4–6 s; normal or complex anatomical structures, pathological processes and their anatomical relationships can be precisely imaged [3, 4]. Finally, on the 16-slice MDCT scanner, by applying the “Combiscan” protocol (0.75-mm collimated scans after administration of intravenous contrast medium), postprocessing of the original data pool can additionally generate high-resolution images of the chest.
Technicalities for MDCT of the paediatric airways
Imaging of the airways and thoracic vessels in infants and children has been significantly affected by the wide spectrum of applications of 16-slice MDCT. The key achievement with MDCT is the increased volume coverage per time unit at high axial resolution, which results in improved temporal resolution. With MDCT, scanning techniques may vary when different collimation is selected: the narrowest collimation is applied when partial volume effect needs to be minimal and the 3-D postprocessing images of optimal quality, e.g. CT angiography (CTA) and cardiac CT [3].
Preparation of the child: is sedation always needed?
Due to the faster scanning times possible with MDCT scanners, routine sedation is no longer required. In the neonate, recent feeding usually provides tranquillity while children over 3 years of age tend to cooperate after explanation of the procedure through play therapy and verbal reassurance. As a result, CT waiting lists have shortened.
Which protocol should be applied?
Planning the examination protocol is essential as this will provide the optimal imaging results that will lead to an accurate diagnosis. Suggested paediatric protocols applied in our institution are displayed in Tables 1, 2, 3, 4 and 5.
Table 1Imaging protocol for the paediatric chest using a 16-row MDCT scanner Routine scanCombiscan/CTAIndicationStrictureCardiovascular anomaliesTumourSmall tracheobronchial stenosesTracheomalaciaPeripheral airways diseaseAnatomical areaThoracic inlet to diaphragmTube collimation (mm)1.50.75Slice width – reconstructed (mm)53Table feed (mm/rotation)2412Exposure factors100 kVp100 kVp20–75 effective mAs (dependent on patient weight)20–75 effective mAs (dependent on patient weight)0.5 s scan time0.5 s scan timeRespirationSuspended inspiration; single breath-hold where possibleThree to five expiratory scans for tracheomalacia/small airways diseaseContrast mediumNoneYesTriggering for CTAAlgorithmSoft tissueSoft tissue plus reconstruction on bony algorithm for high-resolution CT of the lungsTable 2Suggested delay times from the injection of contrast medium Manual injectionPressure injectorScan initiationtime delay10 s from termination of injection25 s from start of injectionFlow rate2 ml/sAge rangeAll age groupsAll age groupsTable 3Volumetric CT chest scanning parameters according to child’s weight when routine and Combiscan protocols are performed <15 kg15–24 kg25–34 kg35–44 kg45–55 kgVolumeCombiVolumeCombiVolumeCombiVolumeCombiVolumeCombikVp100100100100100100100100100100Effective mAs20202525353555557575Collimation (mm)1.50.751.50.751.50.751.50.751.50.75Scan slice width (mm)5555555588Table feed (mm)24122412241224122412Scan time (s)0.50.50.50.50.50.50.50.50.50.5Calculated Effective Dose (mSv)–CT EXPO0.91.01.131.311.581.752.482.753.383.75Table 4High-resolution CT chest scanning parameters according to child’s weight <15 kg15–30 kg>30 kgkVp100100100Effective mAs203055Collimation (mm)111Scan slice width (mm)111Table feed (mm)101010Scan time (s)0.360.750.75Calculated Effective Dose (mSv)–CT EXPO0.210.320.59Table 5CT angiography scanning parameters according to child’s weight <15 kg15–24 kg25–34 kg35–44 kg45–55 kgkVp100100100100100Effective mAs2025354050Collimation (mm)0.750.750.750.750.75Scan slice width (mm)11111Table feed (mm)1515151515Scan time (s)0.750.750.750.750.75Calculated Effective Dose (mSv)–CT EXPO1.01.261.762.02.5
Radiation dose
When dealing with children, the issue of performing a low-dose examination is crucial and of the utmost importance. Radiation dose is a significant issue in paediatrics as it is well established that the life-time cancer mortality risk attributable to CT examinations is considerably higher than in adults [1, 2]. As proposed by the ALARA principle, the selection of appropriate scanning parameters focuses on the optimization of the image quality whilst delivering the lowest possible radiation dose and shifting the risk–benefit balance towards benefit [1, 2, 5].
Technical parameters that need to be selected for any scan include: thickness of collimation, tube current, and kilovoltage. The thickness of collimation is the minimum section thickness that can be acquired once the scan is finished and in a 16-row MDCT scanner is usually 1.5 mm. Thinner collimation (0.75 mm) increases the radiation dose by approximately 30% with our in-house reduced protocol and is applied only in selected cases of vascular abnormalities, visualization of small structures and in cardiac CT (Tables 1 and 6). The axial images are reconstructed at 5-mm thickness and archived to the PACS system within our hospital. In recent years we have made efforts to standardize low-dose protocols for the children scanned in our institution, and the currently applied parameters are summarized in the Tables 1, 3, 4 and 5. Methods adopted to minimize radiation dose in MDCT include:
Applying a dose modulation function, where the system samples the patient thickness and adjusts (i.e. reduces) the exposure accordingly when the tube is in the AP/PA position, as patients are narrower in the frontal than in the side-to-side orientation.Reduction of the kilovoltage to 100 kVp when imaging the thorax. Further reduction to 80 kVp is possible for CTA, but as resolution of the parenchyma is not ideal this is applied only if lung pathology is unlikely.Selecting tube collimation of 1.5 mm. The 0.75-mm collimation improves spatial resolution but, as already mentioned, increases the radiation dose, and is therefore reserved for CTA or where thin-slice reconstruction is indicated.Selecting appropriate mAs selection dependent on the patient’s weight or cross-sectional diameter.Table 6Dose comparison for different scanning protocols in a phantom study in our institutionWeight range (kg)Effective dose (mSv)Volume (1.5 mm)Combi (0.75 mm)High-resolution CTCTAChest radiographyMaleFemaleMaleFemaleMaleFemaleMaleFemaleAPLateral<150.770.900.91.050.360.421.301.510.004870.0079915–240.931.091.131.310.360.421.621.890.008740.0108625–341.341.561.581.840.540.632.242.620.011630.0096835–442.112.462.482.891.001.172.573.00.017690.01452
Unlike the single-slice scanner, an increase or decrease in table feed time on the MDCT scanner only affects the overall scanning time. An increase in table speed results in a concomitant increase in mA and this has no effect on the dose delivered. The tube current is automatically compensated to ensure that the preset effective and total mAs is delivered, i.e. a fast table movement results in an automatic increase in the mA keeping the mAs constant.
Anatomical coverage
For imaging of the paediatric thorax, regular coverage extends from the thoracic inlet to the diaphragm. Greater coverage may be warranted in certain clinical cases, such as an extralobar pulmonary sequestration that may derive its blood supply from the upper abdomen.
In order to increase spatial resolution, the field of view (FOV) should closely approximate the cross-sectional area of the body part being studied. A large FOV would result in waste of matrix space and partial volume averaging would generate poor quality images [2].
Breathing during scan
Ideally, scans should be performed during suspended inspiration at total lung capacity, but this is not often possible in younger children. Experience has proved quiet breathing to be more successful than the confusion created over attempts to acquire the scans during suspended inspiration [6]. When subtle air-trapping due to small airways disease is suspected, a few supplementary expiratory sections may be obtained. If the child is too young to breath-hold, decubitus scans may replace expiratory scans, the dependent lung behaving as the “expiratory” lung and the nondependent lung behaving as the “inspiratory” lung [6]. The acquisition of prone scans is rarely required in older children who may demonstrate hypoventilation changes in the dependent areas of the lungs. General anaesthesia is therefore applied only in a limited number of cases.
Contrast medium
When imaging the airways, intravenous nonionic contrast material is only administered if paratracheal abnormalities, such as vascular rings, anomalous origin of the pulmonary artery, and mediastinal masses are suspected [2]. “Combiscans” provide the potential to image equally well the lung parenchyma by using the high-resolution techniques (HR) for reconstruction algorithms and the mediastinal structures by injecting contrast medium. However, since 0.75-mm fine collimation is required, there is an inevitable increase in the radiation dose (Table 6) and its application is limited to cases where lung parenchymal detail is of high importance.
An intravenous cannula should preferably be placed in situ on the ward so that the child will not associate CT with venepuncture, especially in those in whom subsequent scans may be required. It is ideally inserted via a peripheral vein of the upper or lower limb. Central lines are used for injection in conjunction with clinical agreement and are more desirable as the experience is less unpleasant for the child than having to undergo repeated cannulation. Nonionic contrast medium is administered at a dose of 2.0 ml/kg up to a maximum of 50 ml via a 20/22G cannula using either a power injector or hand injection (when the cannula is placed in the hand or the wrist). The power injector has the advantage of instilling contrast medium at a constant delivery rate. A flow-rate of 2.0 ml/s is used rising to 2.5 ml/s for cardiac studies. The delay time between the start of injection and the start of the scan can be empirical and bolus tracking is routinely used in cardiac CT studies (Table 2).
In children with complex vascular anatomy, the radiologist should be present for the examination. In those children, low-dose planning scans are performed at a predetermined anatomical level and the injection of contrast medium is triggered by the radiologist. The volumetric scan begins when the contrast medium has reached the relevant preselected vascular structure.
Postprocessing
There are four reconstruction displays available for postprocessing of the volumetric data, which are applied accordingly: multiplanar reformation or reconstruction (MPR), 3-D shaded-surface display (SSD), multiprojective volume reconstruction (MPVR) and 3-D volume rendering (VR). In fact, the axial images include all the information about the anatomy of the airways that is provided with 2-D and 3-D reformats. However, postprocessing gives added value to imaging since the axial scans that need to be studied are usually numerous, and oblique structures as well as interfaces and surfaces parallel to the axial plane are poorly demonstrated and sometimes occult.
Multiplanar reformations
These provide additional diagnostic information in different planes and are as accurate as the axial scans due to the nature of the isovolumetric acquisition of the data [3]. MPRs are one-voxel-thick 2-D tomographic sections that can be displayed in coronal, sagittal, or parasagittal planes or in a single tomographic “curved” plane, along the axis of a structure of interest, e.g. a bronchus or a feeding vessel (Figs. 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10) [2, 3]. They are real-time easy-to-reconstruct images, producible as soon as the axial sections are completed. They generally improve our perception of images and give information that although contained in transverse images, is sometimes less effectively displayed. Their diagnostic value is substantial in demonstrating and documenting the presence of small focal lesions, defining the vertical extent of a bronchial stenosis, which may go undiagnosed from the axial source CT images (Figs. 4, 5 and 6), and are invaluable prior to surgical remodelling of vascular rings and the tracheobronchial tree [3]. However, to avoid misinterpretations due to partial volume effect, e.g. overestimation of the degree of a stenosis, overlapping and thinner cuts should be applied when processing the raw data. Likewise, when processing curved MPRs, the trace should be centred within the lumen of interest to avoid anatomical distortion.
Fig. 1Coronal oblique MPR in 4.5-month-old boy with trisomy 21. There is right lung hypoplasia and diaphragmatic eventration. An incidental finding is an aberrant right subclavian artery (arrow)Fig. 2Coronal MPR of the chest in a child with a history of recurrent infections due to a congenital pulmonary airway malformation. A thin-walled multicystic lesion in the right lower lobe is shownFig. 3Combiscan in an 11-month-old child with a congenital pulmonary airway malformation in the right lower lobe. a Coronal MPR in lung window setting shows the air-filled cystic component of the lesion. b, c Axial CT slice (b) and coronal MPR (c) showing a large arterial feeder (arrow). This is, however, visualized and appreciated better with an oblique MIP along the axis of the vessel (d) and with coronal anterior and posterior 3-D VR (e). These images additionally demonstrate the pulmonary venous drainage of the lesion, i.e. intralobar sequestration (curved arrows)Fig. 4Congenital tracheal stenosis in a 3-year-old girl with trisomy 21. a Series of axial slices demonstrating stenosis in the central third of the trachea. b This is more sensitively demonstrated on coronal MPR, which correlates well with the bronchographic appearances(c) (arrows). d Virtual bronchoscopy also demonstrates mild stenosis of the supracarinal portion of the trachea (arrowheads)Fig. 5Chest CT (1.5 mm collimation following intravenous injection of contrast medium) in 10-month-old boy with recurrent wheezing due to congenital tracheal stenosis treated previously with tracheoplasty. There is mild stenosis of the trachea and the origin of the right main bronchus, which is appreciated with difficulty on the axial scans(a), but is nicely shown in coronal MPR (arrow) (b). Virtual bronchoscopy in this case was unnecessary. Bronchography (c) and bronchoscopy confirmed stenosis in the right main bronchus (arrow) that was caused by granulation tissueFig. 6Cardiac CT (0.75 collimation after intravenous injection of contrast medium) in a 6-month-old girl with absent pulmonary valve syndrome. a Axial contrast-enhanced CT shows massive dilatation of the main and the left pulmonary arteries with possible compression of the left main bronchus. This is also appreciated on serial oblique MIPs (b), but becomes more apparent on the oblique MIP along the axis of the left main bronchus (c) (black arrow) and on the 3-D VR (d) (white arrow)Fig. 7Combiscan of the chest in 15-year-old girl with laryngeal/pulmonary papillomatosis. a There is irregular thickening and narrowing of the proximal tracheal wall that is well demonstrated on axial imaging. b, c Coronal MPRs additionally demonstrate intrapulmonary cavitating lesions. Same findings are impressively demonstrated on 3-D VR (d)Fig. 8Myofibroelastic tumour in a child with a history of cough and haemoptysis. Axial imaging (a) and coronal (b) MPR demonstrate infiltration of the right main bronchus from a heterogeneous soft-tissue massFig. 9Coronal MPR shows in detail the extent of the pneumomediastinum with associated surgical emphysema and right pneumothorax in a child with severe combined immune deficiency (SCID) and Pneumocystis carinii pneumoniaFig. 10Coronal MPR in lung window setting demonstrates left lower lobe bronchiectasis (arrow) in a boy with a history of chronic aspiration
3-D imaging
This is a diagnostic tool only in certain cases as it usually requires more time and postprocessing skills to provide information already included and demonstrated in the axial images and the MPRs. There is no doubt, however, that the 3-D reformatted images may further increase the diagnostic confidence which eventually affects patient management, particularly pertinent in presurgical assessment. Communication with the referring clinicians is simplified as the images portray the spatial relationships of important anatomical structures.
3-D shaded-surface display techniques
These are only applied in the imaging of the central airways and they are usually more visually impressive than clinically useful. Their generation from original data is time-consuming and they carry the risk of loss of density information due to problems with thresholding.
Multiplanar volume reconstructions
These are “selective” 3-D images that resemble the 2-D MPRs and depict peripheral airways better than individual sections. With this technique, a combination of the spatial resolution of thin sections and the anatomical display of thicker slices is achieved, and all the information acquired in the raw data set is used. The routine CT images are combined in multiples to create an image thicker in voxels, the volume “slab”, which constitutes an interactive sum of axial, coronal and sagittal reconstructed sections [2, 3]. By using different algorithms and setting thresholds, maximum or minimum intensity voxels can be highlighted within the slab. For the evaluation of the airways, minimum intensity projections within the slab are usually applied (Fig. 11) [2]. Slabs are useful in detecting and localizing micronodular or microtubular patterns and in analyzing mild forms of uneven attenuation of the lungs [7]. However, they are time-consuming and should be reserved for cases of complex morphology, to give the clinicians a comprehensive multilevel roadmap 3-D image.
Fig. 11Complete vascular ring around the trachea and the oesophagus formed by a double aortic arch. a Diagrammatic representation of the abnormality. b Corresponding contrast-enhanced axial image at the level of the double aortic arch, the right part being the dominant. c 3-D VR image of the double aortic arch from a left anterior oblique view. Volume slab (d) and coronal MPR (e) additionally demonstrate the resulting significant narrowing of the trachea
3-D volume rendering
These represent the main technique for 3-D reformatting of the airways and the vascular structures of the mediastinum. The VR technique is particularly useful for displaying structures that course parallel or oblique to the transverse plane and those that develop or extend into multiple planes [2, 3]. However, preliminary editing is still necessary and can be time consuming, altering work patterns in CT. In VR, different anatomical tissues are represented by proportional values that are assigned to every voxel and depend on the range of tissue attenuation values in the original data set. Voxels are selected by the probability of belonging to the object of interest; thus they are displayed in different colours or several shades of grey, different transparency or opacity. Transition from the reconstructed surface to the surrounding media is gradual and the depiction of interfaces, like the inner tracheal lining, is supposed to approach their true appearances. Although this 3-D segmentation technique is better and more complicated than the others previously mentioned, some information is lost during processing, so that the axial images are still indispensable for the radiologist to assess extraluminal disease and identify artefacts. Three-dimensional VR-reconstructed images are attractive and appealing to the clinicians as they may better illustrate short focal areas of narrowing, the craniocaudal length of a tracheobronchial stenosis, and complex congenital cardiovascular and tracheobronchial anomalies (Figs. 2, 3, 6, 7, 11, 12).
Fig. 12a Contrast enhanced 16-slice MCDT (0.75-mm collimation) showing marked tracheal narrowing and an aberrant origin of the left pulmonary artery from the right pulmonary artery (pulmonary sling). b 3D VR demonstrating an elongated and stenotic trachea with identification of a separate bronchus for the right upper lobe
Virtual bronchoscopy
The inner surface of the air-containing tracheobronchial tree can be displayed with virtual bronchoscopy (VB), which is performed with either polygonal SSD or direct VR. VB is a noninvasive and accurate technique that can provide “bronchoscopic” views of the central and the peripheral airways (Figs. 4 and 13). This technique, like fibreoptic bronchoscopy, is considered supplementary to CT and referral to the axial sections is again valuable in recognizing artefacts and in gaining perception of orientation within the virtual airways. VB uses perspective surface rendering, which takes advantage of the natural contrast between the airway and the surrounding tissues [1]. The point for viewing is located intraluminally so that external structures do not overlap and editing takes shorter time periods. Sub-millimetre (0.75 mm) slice thickness allows deeper penetration and visualization of the bronchial surface down to bronchial diameters of less than 5 mm; it is, however, associated with an inevitable increase in radiation dose [4].
Fig. 13Accessory bronchus. a Bronchography and b volume rendered 16-slice VB demonstrating an accessory bronchus (curved arrows). On the MDCT image at the level of the carina, a more cephalad origin of the apical accessory bronchus isnoted
Again, VB practically never really adds anything new to the established diagnosis. However, pulmonologists may prefer and relate to these images in conjunction with the axial or the reformatted ones [2]. In practice, VB is of limited value, reserved for cases where bronchoscopy is not applicable (children in whom traditional bronchoscopy presents a risk) or precise navigation is not possible to guide airway interventional procedures, and in emergencies such as infant airway (tracheal) stenosis which cannot be otherwise evaluated [4]. The images produced resemble the actual bronchoscopic ones and can additionally “advance” distal to an airway obstruction, where the real endoscope cannot penetrate [3, 8]. However, when compared to fibreoptic bronchoscopy, VB does not allow any therapeutic manoeuvring, is incapable of detecting endoluminal lesions smaller than 2–3 mm that may go undetected due to the partial volume effect, and provides limited information about mucosal detail (morphology, vascularity and colour), making differentiation between pathological processes and retained secretions difficult [1–4, 9, 10]. There is consensus that measurements should be performed only on 2-D sections as they may otherwise be inaccurate [3, 8]. The technique is additionally affected by the partial volume effect, which may lead to misinterpretation of severe stenoses as occlusions, and the threshold level is therefore of importance for displaying accurate simulations [8].
Dynamic and functional inspiratory and expiratory scanning
In conjunction with single-breath-hold MDCT, dynamic and functional inspiratory and expiratory scanning helps identify strictures, areas of air-trapping and tracheobronchomalacia, but is rarely applied in paediatric practice because of the associated radiation burden [2].
Peripheral airways
Modern volumetric techniques have partially overcome the difficulty in demonstrating 3-D images of the peripheral airways. Data are acquired and reconstructed at a later time, allowing thin-slice high-resolution images at any level, so that a whole affected bronchiectatic segment can be displayed on a single MPR/VR oblique section (Fig. 10) with images that resemble conventional bronchography and may influence the approach for tissue sampling [3, 7]. If there is suspicion of small-airways disease, some additional expiratory slices may be useful. Whatever the application we perform, all the techniques are considered as an adjunct to conventional HRCT evaluation of the peripheral airways that allows accurate and precise assessment of diffuse lung disease at very low doses equivalent to approximately ten chest radiographs [3, 6].
Clinical applications of volumetric imaging of the airways in children
Selection of the most appropriate CT protocol for each individual case is paramount in imaging of the airways in children. Ultimately, the best protocol is the one that provides the most relevant information at the lowest radiation burden possible. The indications include: (1) congenital bronchial anomalies (e.g. accessory bronchi, bronchial hypoplasia and atresia, and bronchopulmonary foregut malformations), (2) tracheomalacia, (3) tracheobronchial strictures (congenital and acquired) or tumours, and (4) peripheral (small) airways disease.
Tracheobronchial anomalies
Approximately 1–12% of adult patients who undergo bronchoscopy demonstrate some form of congenital variant [1, 11]. Tracheobronchial anomalies may be associated with recurrent episodes of pulmonary infection and airway obstruction and usually go undiagnosed with conventional imaging [1, 12].
Tracheal bronchus
Tracheal bronchus, with an incidence of 0.1–5%, represents an aberrant bronchus that usually arises from the right tracheal wall above the carina and ventilates the apical segment of the upper lobe (Fig. 13) [1, 13]. If the right upper-lobe bronchus has a normal trifurcation then the tracheal bronchus is supernumerary and may end blindly; it is also called a tracheal diverticulum. Left tracheal bronchus has also been reported [13]. Its presence may be associated in some patients with other abnormalities of the lung or within the spectrum of the VACTREL (V vertebral, A anorectal atresia, C cardiac, T tracheobronchial, R renal, E esophageal, L lumbosacral/limb abnormalities) association. Diagnosis of tracheal bronchus should be considered early in the clinical course of intubated patients with recurrent right upper-lobe complications [11]. Coronal MPRs are particularly helpful in demonstrating the presence of a tracheal bronchus, which may go undetected on axial images. Findings can be additionally supported with VB.
Bronchial atresia
Bronchial atresia may present with a variety of findings depending on the child’s age (water-density mass in newborns, bronchocele and air-trapping during childhood, and solitary pulmonary nodule or area of emphysema in adults). In doubtful cases, MPRs help identify mucoid impaction and bronchocele as a branching structure radiating from the hilum [13].
Bronchopulmonary foregut malformations
These are anomalies of pulmonary development that are due to abnormal budding of the embryonic foregut and tracheobronchial tree. They include duplication cysts characterized by an isolated portion of lung tissue communicating with the upper gastrointestinal tract or the central nervous system such as bronchogenic cysts, enteric cysts, and neurenteric cysts. Symptoms are usually provoked by the size and location of the cysts, which may cause compression of the trachea or bronchi leading to distal collapse and air trapping. Infection is less commonly encountered.
Pulmonary underdevelopment
The spectrum of pulmonary underdevelopment includes agenesis of the bronchus and lung (pulmonary agenesis), presence of a rudimentary blind-ending bronchus without lung tissue (pulmonary aplasia) and bronchial hypoplasia with reduction of lung tissue of variable degree (pulmonary hypoplasia) (Fig. 1) [13].
Scimitar syndrome
The scimitar syndrome, also called venolobar syndrome and hypogenetic lung syndrome, is a rare congenital cardiovascular anomaly involving the right lung. It consists of ipsilateral anomalous pulmonary drainage of part of the right lung into the inferior vena cava, hypoplasia of the right lung, dextrorotation of the heart, hypoplasia of the right pulmonary artery, and anomalous systemic arterial supply to the lower lobe of the right lung from the subdiaphragmatic aorta or its main branches. It may be associated with abnormal bronchial anatomy, abnormal diaphragm, hemivertebrae, and anomalies of the genitourinary tract. CT with MPRs shows the size of the right hemithorax, the associated bronchial anomalies, and the anomalous pulmonary (scimitar) vein [13].
Sequestration spectrum
The sequestration spectrum includes congenital pulmonary airway malformations (CPAMs), anomalies previously termed congenital cystic adenomatoid malformations, the pulmonary sequestrations and also hybrid lesions that histologically consist of both entities (Figs. 2 and 3). CT defines their location, extent and anatomical relationships, and evaluates their density. MPRs and VRs can impressively demonstrate the arterial feeder from a subphrenic aortic branch and detect the venous drainage into the systemic or pulmonary circulation for the extra- and intralobar sequestrations, respectively (Fig. 3). Enhancement of the cystic wall implies infection.
Tracheomalacia
Tracheomalacia is a condition that refers to softening of the tracheal wall. This is caused from an abnormality of the cartilaginous ring and hypotonia of the myoelastic elements. There is dynamic collapse of the trachea during expiration which leads to airway obstruction with development of wheeze, cough, stridor, dyspnoea, cyanosis and recurrent respiratory infections. Primary tracheomalacia is thought to be caused by congenital immaturity of the tracheal cartilage and may be associated with other developmental defects, such as a vascular ring/compression or tracheo-oesophageal fistula. The natural history shows that it improves by the end of the first year. In secondary tracheomalacia, previously normal cartilage undergoes degeneration [13].
Tracheobronchial strictures
Congenital tracheal stenosis
Congenital tracheal stenosis is a rare disorder characterized by a fixed tracheal narrowing caused by complete tracheal cartilage rings (Fig. 4). Approximately 50% of congenital tracheal stenoses are focal, located usually in the lower third of the trachea, 30% are generalized and 20% are funnel-shaped [13]. The bronchi are usually of normal size. This abnormality which may be associated with other anomalies, more commonly pulmonary artery sling, should be suspected when a distal tracheal stenosis is recognized in an infant [13].
Congenital lobar emphysema/overinflation
Areas of malacia or stenosis of the bronchial cartilage are thought to be the aetiological factors in the development of congenital lobar emphysema/overinflation through a check-valve mechanism, which is characterized by progressive distension/hyperinflation of a lobe, most commonly the left upper lobe. CT will typically show hyperinflation of the affected lobe without destruction of the alveolar walls and will help to differentiate this condition from others (Fig. 14).
Fig. 14Axial CT of an infant with mediastinal shift shown on a chest radiograph showing hyperinflation of the left upper lobe without destruction of the alveolar walls, consistent with congenital lobar emphysema
Acquired tracheobronchial stenoses
Acquired tracheobronchial stenoses may result from prolonged intubation (post-intubation webs) or at the anastomosis sites following surgical intervention/lung transplantation. In patients in whom the axis of the stenosis is vertical or slightly oblique it is usually difficult to perceive on the axial images alone, and MPRs/VRs are useful adjunctive tools (Fig. 5).
Compression of the airways of cardiovascular origin
This is a relatively common complication of cardiovascular diseases that may go unrecognized for some time. Compression is caused either because of an underlying anomalous anatomical relationship between the tracheobronchial tree and the vascular structures, e.g. a double aortic arch, or is extrinsic, caused by enlarged cardiac or pulmonary vascular structures, e.g. congenital heart disease, dilated pulmonary arteries (Fig. 6). In children with unexplained respiratory distress, stridor, wheezing, dysphagia and apnoea, a high index of suspicion is required to identify these lesions that cause mechanical airway compression [14, 15].
A vascular ring is an aortic arch anomaly in which the trachea and the oesophagus are completely surrounded by vascular structures. They are formed because components of the aortic arch complex persist or regress abnormally. If the airway is incompletely encircled then a vascular sling is produced [13–15].
The most common and clinically serious type of vascular ring is the double aortic arch, which represents a persistence of both right and left embryonic fourth arches joining the aortic portion of the truncoaortic sac to their respective dorsal aortae [14]. It typically consists of a right and a left arch that encircle the trachea and oesophagus in a tight ring, joining distally to form a common descending aorta (Fig. 11). Variations of this anomaly have been reported, e.g. hypoplasia of one arch [13].
Another vascular sling can be produced by an abnormal origin of the left pulmonary artery from the right pulmonary artery (Fig. 12). As the former crosses to the left, it encircles and compresses the right main bronchus and the trachea and occasionally the left main bronchus. This condition is usually associated with other congenital anomalies [14].
Foreign body aspiration
This is one of the most common and potentially life threatening events in children, accounting for 7% of lethal accidents in infants aged 1–3 years [16]. MDCT of the chest for the detection of radiolucent foreign bodies is not the investigation of first choice and not routinely used unless a pulmonary infiltrate that fails to resolve within the normal recovery period of 10–14 days is present [16]. It is vital to remember that actual bronchoscopy should be performed even in cases of low clinical suspicion and no direct history since the risk of overlooking foreign body aspiration may be lethal and may cause long-term pulmonary damage.
Local extension of neoplasms
MPRs/VRs with coevaluation of the axial images are the method of choice for staging of hilar or mediastinal neoplasms. They demonstrate interfaces accurately, e.g. the relationship of the lesions to the bronchovascular walls and the presence of mediastinal lymph nodes, since they maintain voxel density values (Figs. 7 and 8). More complex rendering techniques are not usually required [3].
Peribronchial air collections
MPRs/VRs are helpful in demonstrating small extraluminal air collections and leakages of surgical anastomoses, especially in orthotopic lung or heart/lung transplant patients (Fig. 9). They can impressively show fistulous paths that may be indiscernible on axial images and affect patient management [3]. Additionally, by correlating with VB the precise location of the leak can be traced prior to actual bronchoscopy.
Peripheral airways
MPRs/VRs using MDCT technology have achieved more accurate visualization of the distal airways. The VR technique is applied in thin, overlapping, transverse reconstructed sections using a high-resolution algorithm. This is particularly helpful in the search for bronchiectasis where a single oblique MPR/VR section may include the whole portion of the affected bronchi (Fig. 10). Additionally, when planning the best approach for tissue sampling the relation between peripheral nodules and the afferent bronchus is better appreciated using the MIP/VR sections. Although the applications of conventional HRCT for the evaluation of the peripheral airways are beyond the scope of this review article, the value of HRCT should not be overlooked. When performed individually, HRCT is considerably less of a radiation burden than MDCT (Table 6), but with the standard HRCT protocol, limited slices are performed and the imaging of the mediastinum is insufficient. On the contrary, the Combiscan MDCT protocol with the possibility of HR reconstructions allows detailed parenchymal evaluation of the whole of the chest and simultaneous imaging of the mediastinum; however, there is the disadvantage of extra radiation burden (Table 6).
Conclusion
MDCT with 2-D and 3-D reconstructed imaging has enhanced the applications of CT in imaging of the chest in children. Obtaining high-quality scans should always be attempted at the lowest radiation dose possible. CT and bronchoscopy are supplementary examinations in the diagnostic work-up of children with tracheobronchial pathology. Although 2-D and 3-D rendering techniques are not the first-line diagnostic tools, they significantly reinforce the confidence in a diagnosis even in complex cases. In specific scenarios, they may supply information that is more easily interpreted among the different specialties than conventional axial scans. In the future, virtual tracheobronchial endoscopy is anticipated to be applied for interactive virtual-reality guidance in surgical procedures of the airways.

tracheobronchial tree
children
volumetric
multidetector ct


Experience of robotic catheter ablation in humans using a novel remotely steerable catheter sheath

Background A novel remotely controlled steerable guide catheter has been developed to enable precise manipulation and stable positioning of any eight French (Fr) or smaller electrophysiological catheter within the heart for the purposes of mapping and ablation.
Introduction
Mapping and catheter ablation of cardiac arrhythmias can be technically complex and challenging. Currently the majority of such procedures are performed using manually deflectable catheters. These catheters have limited range and flexibility and rely on operator skill to manoeuvre the catheter tip and maintain stability at target sites within the heart.
A novel electromechanical master/slave system that can remotely control a steerable guide catheter (Hansen Medical, Inc., Mountain View, CA, USA) has been developed to enable precise positioning and manipulation of any type of electrophysiological catheter within the heart for the purposes of mapping and ablation. The system comprises three linked components: the physician’s workstation (Sensei™ robotic control system), remote catheter manipulator (RCM) and steerable guide catheter (Artisan™ Control Catheter) (Fig. 1).
Fig. 1The remote catheter manipulator (RCM) (left) is attached to the steerable guide catheter (Artisan™) through which a mapping catheter can be positioned within the heart. The physician’s workstation (right) navigates the steerable guide catheter remotely
The physician’s workstation
The physician’s workstation consists of display screens for contact intracardiac electrophysiology data and 3D mapping systems as well as a central fluoroscopic control view also displaying a superimposed icon of the Artisan Control Catheter (Fig. 2). Integral to the workstation and its control of the Artisan is the Instinctive Motion Controller (IMC); effectively a 3-dimensional hand operated joystick. The position of the IMC handle is calculated from internal sensors, and this position is fed to control computers in a separate electronics rack which in turn guides the remote catheter manipulator (RCM).
Fig. 2The Instinctive Motion Controller (top left) used with a control panel on the physician’s workstation (bottom left) remotely guides the steerable guide catheter which can be seen on the central “control view” display (right). Real-time data on catheter orientation, catheter-tip pressure, fluoroscopic views as well as intracardiac echocardiography are shown
Remote catheter manipulator
The RCM is a robot designed to accept the Artisan catheter. The RCM receives catheter position commands from the control computers as issued by the IMC. Acting on these commands, the RCM uses servo motors to control its motions. These motions transfer to the Artisan catheter’s pull wires, ultimately determining the position of the catheter tip.
Steerable guide catheter (Artisan)
The Artisan is a single use sterile guide catheter that is composed of two parts: a steerable inner guide within a steerable outer guide (Fig. 3). The outer guide catheter (outer size 14 Fr, inner size 11 Fr), controlled by two pull wires 180° apart, provides a stable base for the inner guide (11 Fr outer, 8.5 Fr inner). Four orthogonal pull wires deflect the inner guide catheter in x and y direction so it can reach anywhere within a roughly toroidal workspace defined by bend of up to 270° and 10 cm extension. Both sheath movements are controlled by the operator. Combined with the RCM’s ability to insert the entire Artisan forward and rotate it, the tip has a versatile reach. Conventional 8 Fr or smaller mapping and ablation catheters are inserted through the inner guide catheter and locked in place at the proximal end of the Artisan. The deflection mechanisms of these catheters are not required and remain within the Artisan. The only part of the catheters to protrude from the tip of the Artisan control catheter are the distal bipole and occasionally the proximal bipole, as determined by the operator on insertion of the conventional catheter into the Artisan.
Fig. 3The Artisan control catheter and its components. SIG Steerable inner guide, SOG steerable outer guide
We report our initial experience in testing the hypothesis that robotic remote catheter ablation in humans is feasible and safe using existing catheters and mapping systems. This study was approved by St. Mary’s Hospital local ethics committee.
Materials and methods
Consecutive patients meeting inclusion criteria and without exclusion criteria (Table 1) were recruited. As part of the initial safety protocol, ten patients underwent remote mapping only and these patients subsequently underwent conventional ablation after the steerable guide catheter was removed. A further ten patients underwent both remote mapping and ablation using the Artisan, the results of which are presented in this paper. Informed written consent was obtained from all patients prior to the procedure. All were studied in the fasted state with or without intravenous sedation.
Table 1Inclusion and exclusion criteriaInclusion criteriaExclusion criteriaSuitable for catheter mapping/ablationSevere cerebrovascular disease18–85 years of ageSerum creatinine > 2.5Body Mass Index < 40Active gastrointestinal bleedingSigned informed consentActive infection or feverShort life expectancy <1 yearSignificant anemiaSevere electrolyte imbalanceAllergy to contrastCongestive heart failure (NYHA Class IV), ejection fraction <30%Unstable angina requiring emergent percutaneous interventionRecent myocardial infarction within 2 weeksBleeding or clotting disordersUncontrolled diabetesInability to receive IV anticoagulants
Various diagnostic catheters were inserted and manipulated manually through the left femoral vein for initial arrhythmia mapping. These included Josephson™ quadripolar catheters in combination with Cardima™, Halo™ and Lasso™ catheters for mapping a left lateral accessory pathway, two atrial flutter circuits and for seven atrial fibrillation ablation procedures respectively.
Transeptal access was performed to treat the patients with an accessory pathway and atrial fibrillation. In the cases of atrial fibrillation ablation, a single transeptal puncture was made from the left femoral vein, the needle was removed, the sheath withdrawn into the right atrium and an .035 J-wire left across the puncture site. The Artisan containing the ablation catheter was then guided from the right femoral vein through the puncture site into the left atrium for ablation. It is useful to note that although the outer guide is able to cross the inter-atrial septum, for the majority of cases, this remains on the right atrial side of the septum and catheter navigation within the left atrium was done mainly using the inner sheath. The pulmonary veins were mapped manually with a Lasso™ placed via the left femoral transeptal sheath. For left-sided procedures titrated intravenous heparin boluses of up to 10,000 units were given every 30 min to maintain an activated clotting time of at least 300 s.
The Artisan control catheter was inserted into the right femoral vein through a short non-irrigated 14 Fr sheath. Various conventional 4 and 8 mm non-irrigated tip (EPT Blazer II™) and irrigated-tip (Navistar™ Thermocool™) catheters were deployed through the lumen of the Artisan for ablation. Continuous heparinised saline flushing was maintained through the side ports of the inner and outer sheaths of the Artisan.
Conventional mapping was complemented with 3D non-fluoroscopic mapping technologies as required, including NavX™ (St. Jude Medical, St. Paul, MN, USA), CARTO™ and CARTOMERGE™ (Biosense Webster Inc., Diamond Bar, CA, USA).
All 3D maps, computed tomography scan registration, mapping and ablation were performed remotely. In the atrial fibrillation cases some ablation points were ‘drag’ lesions used to construct ablation lines.
Conventional endpoints of loss of accessory pathway function, bidirectional cavotricuspid isthmus block and four pulmonary vein isolation were used to determine immediate procedural success.
At the end of the procedure the Artisan was removed from the 14 Fr venous sheath manually. If heparin had been given during the procedure, intravenous protamine was administered and removal of the 14 Fr sheath was done under manual pressure once the activated clotting time was less than 150 s.
Results
Twenty patients were studied. In ten, only mapping to specific anatomical sites was performed using the Hansen system for regulatory purposes without any procedural complication related to using the system. The other ten patients underwent remote catheter ablation and are the subjects of this report. All mapping and ablation endpoints were achieved using only the Sensei robotic control system, without manual manipulation of the ablation catheter in these ten patients.
Table 2 shows the procedures undertaken, equipment used, radiation exposure, procedural and ablation times. (Note that ablation times are taken from the first application to the last application of radiofrequency energy. All RF applications were given for up to 1 min at a time). Figures 4 and 5 show examples of the use of the steerable catheter in combination with each mapping system.
Fig. 4Examples of the use of the remotely controlled catheter sheath in conventional electrophysiological procedures. LAO projection of a left free wall accessory pathway ablation (left) and PA projection of segmental right upper pulmonary vein isolation (right). (SGC steerable guide catheter, Abl ablation catheter tip)Fig. 5Non-fluoroscopic mapping system images created using the remotely controlled steerable guide catheter. Anteroposterior view of the left and right atrial geometry using NavX™ (top left) and posteroanterior view of the left atrium during wide area circumferential ablation using CARTO™ (top right). Posteroanterior view of the left atrium (bottom left) and cross-sectional view of the left sided pulmonary veins (bottom right) during segmental pulmonary vein isolation using CARTOMERGE™. (Ablation lesions in red)Table 2Robotic ablation procedural dataPatientSexAgeDiagnosisProcedureMapping systemCatheter tipNumber of RFsRF timeTotal procedure timeFlouro timePatient DAPWorkstation DAP1F76Atrial flutterCTIconventional4 mm irrigated3810314044.58,38302M55Permanent atrial fibrillationPVI, left atrial mazeNavX™4 mm irrigated6319125911624,66703M50Paroxysmal atrial fibrillationPVINavX™4 mm irrigated421111705211,21604M41Accessory pathwayPathway ablationconventional4 mm non-irrigated33110613.477905F71Atrial flutterCTIconventional8 mm non-irrigated15337019.91,04206M53Persistent atrial fibrillationPVI roof line, MINavX™4 mm irrigated3912316555.26,57707M73Persistent atrial fibrillationPVI and roof lineNavX™4 mm irrigated4614316664.24,73908F63Paroxysmal atrial fibrillationPVI and roof lineNavX™4 mm irrigated4811815742.87,27109F46Atrial ectopy/paroxysmal atrial fibrillationPVICARTOMERGE™4 mm irrigated3114312441.72,262010M54Persistent atrial fibrillationPVI and roof lineCARTO™4 mm irrigated6815522343.45,8780[CTI cavotricuspid isthmus line, PVI pulmonary vein isolation, MI mitral isthmus, line, RF radiofrequency ablation. RF time – time from first RF to the end of the last RF. All times are in minutes. Radiation exposures are expressed as dose area product DAP (cGycm2).]
No major complication occurred. One patient (accessory pathway) had a small <1 cm pericardial effusion measured on echocardiogram 24 h post-procedure. The patient was not on post-procedural anticoagulation and was discharged without any clinical sequalae. There were no femoral haematomas associated with the use of the system.
A radiation dosimeter (Mydose Mini X, Aloka Co. Ltd., Japan) positioned at the physician’s workstation approximately 2.7 m away from the X-ray source demonstrated negligible exposure to the operator despite a mean cumulative dose area product of 7,281.4 cGycm2 for all ten ablation procedures.
Discussion
Complex ablation procedures to treat cardiac arrhythmias can be time consuming and technically challenging. There is always a need to improve procedural success, reduce procedure times and minimize fluoroscopy screening times. These issues are largely governed by the skill and efficiency of the operator using manually controlled catheters that may be limited in their flexibility and manoeuvrability. Computer assisted remote catheter ablation systems may minimize some of these difficulties by reducing the manual skill required, potentially reducing the operator’s learning curves.
The potential advantages of remote ablation include improved catheter manoeuvrability, precision and especially stability in areas within the heart which may be difficult to reach manually and the ability to reproducibly and accurately return to sites of interest during a procedure. Another remotely controlled catheter technology in current clinical use involves magnetic tipped catheters that are directed within a magnetic field. Its efficacy has already been demonstrated in mapping and ablation of accessory pathways, atrial, nodal and ventricular arrhythmias [1–5].
Electromechanical systems are an alternative means of remote catheter ablation. An in-depth comparison of the advantages and disadvantages of both systems is beyond the remit of this paper; particularly as robotic catheter navigation has only just been developed whereas magnetic navigation has already established itself in clinical trials. However, one can see the advantages of being able to use a remote navigation system that is portable; does not exclude patients that have metal implants or devices and is compatible with other mapping systems and catheters. It remains to be seen whether robotic navigation can achieve the long-term efficacy and safety of magnetic navigation. In particular, whilst catheter-tip stability is improved, the amount of energy applied and the duration needed to achieve successful ablation without increasing the risk of “pops” and resultant perforation needs to be determined.
Robotic systems have already been used in surgical procedures, demonstrating improved precision, stability and dexterity [6]. Our study has shown that the Sensei robotic system in combination with the Artisan control catheter is safe, feasible and effective in achieving conventional endpoints in mapping and ablation within the human heart.
Safety
Previous studies with porcine models as well as a small human study have shown its safety in vivo [7–9]. A potential problem with a remote catheter control system is the lack of mechanical feedback that one would receive from manually controlling a catheter. This is important in assessing how much force is being applied in moving and maintaining catheter tip position. Knowledge of this force is important in avoiding damage to or perforation of cardiac and vascular structures. A system called Intellisense™ Fine Force Technology uses two force sensors that grip the shaft of the working catheter as it protrudes from the Artisan catheter. The working catheter is pulsed a short distance (<1.5 mm) in and out of the Artisan four times each second and with each pulse, coaxial force data are collected and compared. Forces applied to the working catheter tip are measured and displayed on the main screen as visual feedback of force (Fig. 6). This does not provide feedback on all the multidirectional forces applied to all parts of the catheter and, whilst it would be ideal to receive mechanical feedback through the instinctive motion controller, the visual data provided on the most important part of the catheter helps the operator to overcome this potential problem.
Fig. 6The Intellisense system display (close-up edited view). Coaxial forces sensed at the catheter tip are displayed as a realtime waveform strip chart and gauge. On the strip chart there is a “warning level” threshold which is set by the operator. When forces exceed this level, the tip of the animated catheter changes colour (from white to yellow), and the strip chart plot line changes colour as well
In the authors’ personal experience using this system, although visual representation of the forces applied at the catheter tip is better than none at all, it does not replace the tactile responses that experienced operators use to prevent damage or perforation of cardiac structures. The Intellisense system allows the operator to predetermine what pressure level is deemed to be ‘excessive’ and if pressures exceed this arbitrary threshold the tip of the virtual catheter and the pressure waveform changes colour as a warning but there is no auditory alarm, requiring the operator to be constantly vigilant.
Another potential problem is the potential for thrombus to form within the Artisan’s sheaths. This was avoided by high flow continuous flushing and appropriate heparinisation. No thrombotic complication occurred in this study.
Fluoroscopy and radiation exposure
Complex ablation procedures such as for atrial fibrillation can be lengthy and radiation exposure to both patients and operators remains a concern. The present study does not fully represent the potential for a robotic system to reduce X-ray exposure to patients. For the operator, during conventional ablation procedures, despite adequate radiation protection, areas such as the face and extremities are still subject to scattered radiation exposure which impacts on cumulative dose [10, 11]. Our study has shown that negligible operator radiation exposure can already be achieved from being less than 3 m away from the radiation source whilst still being within the laboratory, potentially reducing the long-term risks to operators from radiation. Once the learning curve is overcome and procedure times improve, when used fully in combination with non-fluoroscopic mapping systems, robotic ablation could potentially reduce patient radiation exposure as well.
Versatility
This study has demonstrated the system’s compatibility with various irrigated and non-irrigated tipped ablation catheters as well as its use with existing non-fluoroscopic mapping systems such as CARTO™ and NavX™. There was no technical difficulty in setting up and performing mapping and ablation in any of the cases. In the case using a Thermocool Navistar 8 mm tip catheter, insertion into the Artisan was not problematic, though the fit prevented the Intellisense force feedback system from moving the catheter tip. Mapping and ablation was performed unhindered but with the Intellisense system switched off.
Limitations
This is a small feasibility study therefore conclusions with regards to overall efficacy and efficiency of the system for each type of arrhythmia cannot be made. For comparison, averaged data from conventional procedures (n = 10 for each) undertaken at our laboratory are shown in Table 3. It should be noted that this data represents the work of several operators of varying skill and experience. The robotic atrial fibrillation data (RF time 140 ± 27 min, procedure time 181 ± 45 min, n = 7) show that times are longer on average compared to conventional procedures. This is not surprising as, with any new device, there is a learning curve to its use.
Table 3Conventional ablation procedural dataAblation procedureNumber RFsRF timeTotal procedure timeFlouro timeDAPAtrial fibrillation–111 ± 51 (44–171)143 ± 52 (45–204)61.4 ± 31 (24–121)6,636 ± 5,867 (1,776–19,489)Atrial flutter7 ± 5 (2–18)21 ± 16 (4–56)62 ± 24 (25–94)23 ± 13.3 (7–49)1,369 ± 1,108 (189–3,596)Accessory pathway3 ± 3 (1–11)14 ± 25 (1–83)97 ± 53 (36–186)22.9 ± 12.2 (9–44)2,899 ± 3,224 (219–11,055)Figures represents data taken from conventional procedures (n = 10) for each arrhythmia type. Means are given with standard deviations and ranges. Times are in minutes. RF—radiofrequency energy lesion. Dose area product (DAP) in cGycm2.
The operators themselves underwent an intensive two day training course to familiarise themselves with the set-up and use of the equipment in animals prior to the study being undertaken. During the animal case the physician is instructed in how to drive to certain places in the right atrium, how to cross the septum and drive to defined points in the left atrium and also how to create a 3D atrial geometry. It is understandable that great caution was employed with its use in the first human subjects. Despite this, the data are sufficient to conclude that the system can work safely and effectively in humans and can achieve conventional endpoints of ablation.
Conclusions
The Sensei robotic control system in combination with the Artisan control catheter is compatible with current mapping and ablation technologies, enabling clinically effective remote navigation of ablation catheters. Remotely controlled catheter ablation for cardiac arrhythmias using this system reduces operator radiation exposure.
Electronic supplementary material
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catheter ablation
remote navigation
robotic navigation