Mechanics of the exceptional anuran ear The anuran ear is frequently used for studying fundamental properties of vertebrate auditory systems . This is due to its unique anatomical features , most prominently the lack of a basilar membrane and the presence of two dedicated acoustic end organs , the basilar papilla and the amphibian papilla . Our current anatomical and functional knowledge implies that three distinct regions can be identified within these two organs . The basilar papilla functions as a single auditory filter . The low-frequency portion of the amphibian papilla is an electrically tuned , tonotopically organized auditory end organ . The high-frequency portion of the amphibian papilla is mechanically tuned and tonotopically organized , and it emits spontaneous otoacoustic emissions . This high-frequency portion of the amphibian papilla shows a remarkable , functional resemblance to the mammalian cochlea . Introduction The anatomy and physiology of the amphibian ear show both remarkable resemblances and striking differences when compared to the mammalian auditory system . The differences between the human and the amphibian auditory system are too significant to warrant direct generalizations of results from the animal model to the human situation . However , studying hearing across species helps to understand the relation between the structure and function of the auditory organs -LRB- Fay and Popper 1999 -RRB- . Thus , we hope and expect that the knowledge gained about the amphibian auditory system fits into our understanding of auditory systems in general . Over the course of history , a number of diverse amphibian species developed . Currently only three orders remain : anurans , urodeles , and caecilians . Their evolutionary relationship , as well as the evolutionary path of the individual orders , is still under debate . However , they are generally grouped into a single subclass , Lissamphibia of the class Amphibia -LRB- Wever 1985 -RRB- . The ancestral lineage of amphibians separated from the mammalian lineage , approximately 350 million years ago , in the paleozoic era . Many of the important developments in the auditory systems emerged after the ancestral paths separated -LRB- Manley and Clack 2003 -RRB- . This implies that shared features , like the tympanic middle ear , developed independently in different vertebrate lineages . The anurans - frogs and toads - form the most diverse order of amphibians . The living species are classified into two suborders , Archaeobatrachia and Neobatrachia -LRB- Wever 1985 -RRB- . Both within and between these suborders , there is a large variation in the anatomy and physiology of auditory systems . The most thoroughly studied species belong to the family Ranidae , as is reflected in the work referenced in this paper . The hearing organs of anurans are often falsely assumed to be more primitive than those of mammals , crocodiles , and birds . The relatively simple structure and functioning of the amphibian ear offer an excellent possibility to study hearing mechanisms -LRB- e.g. , Ronken 1990 ; Meenderink 2005 -RRB- . On the other hand , the sensitivity of the frog inner ear , which appears to be able to detect -LRB- sub -RRB- angstrøm oscillations -LRB- Lewis et al. 1985 -RRB- , shows that the frog ear functions as a sophisticated sensor . While the ears of most vertebrate species contain one dedicated acoustic end organ , the frog ear has two , the amphibian papilla and the basilar papilla . 1 Like in other vertebrates , these organs contain hair cells for the transduction of mechanical waves into electrical -LRB- neural -RRB- signals . In mammals , birds and lizards , the hair cells are set on a basilar membrane . The frog inner ear lacks such a flexible substrate for its sensory cells . The hair bundles of the frog 's auditory organs are covered by a tectorial membrane , as they are in all terrestrial vertebrates except for some lizards species -LRB- Manley 2006 -RRB- . In mammals , the mechanical tuning of the basilar membrane is the primary basis for frequency selectivity . In the absence of the basilar membrane , the frog 's auditory organs must rely solely on the tectorial membrane and on the hair cells themselves for frequency selectivity . Recently , Simmons et al. -LRB- 2007 -RRB- and Lewis and Narins -LRB- 1999 -RRB- published reviews of the frog 's ear anatomy and physiology . In the current paper , we focus on the mechanics of the inner ear , specifically on the mechanics of the tectorial membrane . Only one publication exists on direct mechanical/acoustical measurements of structures in the frog inner ear -LRB- Purgue and Narins 2000a -RRB- . Therefore , many of our inferences will result from indirect manifestation of inner ear mechanics , as observed in anatomical , electro-physiological and otoacoustic-emission studies . Nevertheless , these studies provide a consistent view of the mechanics of the anuran inner ear . Anatomy Middle ear The ears of most terrestrial vertebrates can be divided into three principal parts : the outer ear , the middle ear and the inner ear . In mammals , the outer ear consists of a pinna and an ear canal , which terminates at the tympanic membrane . In most frog species the outer ear is absent , 2 and the tympanic membrane is found in a bony ring , the tympanic annulus , in the side of the skull . The tympanic membrane defines the distal boundary of the middle ear cavity . This air-filled cavity is spanned by the ossicular chain , which serves to transfer vibrations of the tympanic membrane to the oval window of the inner ear . In the frog , the ossicular chain consists of two structures , the extra-columella and the columella -LRB- Jørgensen and Kanneworff 1998 ; Mason and Narins 2002a -RRB- . The cartilaginous extra-columella is loosely connected to the center of the tympanic membrane . Medially , it flexibly connects to the partially ossified columella . The columella widens to form a footplate at its medial end , where it attaches to the oval window of the inner ear . Acoustic stimuli primarily enter the inner ear through the oval window . The middle-ear 's primary function is to compensate for the impedance mismatch between the air and the fluid-filled inner ear . There are two contributions to this compensation -LRB- Jaslow et al. 1988 ; Werner 2003 -RRB- . The first contribution results from the small area of the oval window relative to the area of the tympanic membrane . This causes a concentration of the external force exerted on the tympanic membrane . The second contribution involves a lever action of the columella footplate . The footplate attaches to the otic capsule along its ventral edge . This bond is suggested to be the location of the hinging point of the middle ear lever in the frog -LRB- Jørgensen and Kanneworff 1998 ; Mason and Narins 2002b -RRB- . The lever action serves as a force amplification mechanism and contributes to the impedance matching between the outside air and the fluids in the inner ear . Both effects result in pressure amplification between the tympanic membrane and the columella footplate , thus overcoming the impedance mismatch between air and the inner-ear fluids . An additional bony disk , the operculum , is flexibly attached to the oval window in amphibians . The presence of an operculum in anurans is unique among vertebrates . The operculum 's position in the oval window can be modulated through the m. opercularis , which also connects it to the shoulder girdle . The function of the operculum is not entirely clear . Possibly , it serves to transfer substrate vibrations to the inner ear -LRB- Lewis and Narins 1999 ; Mason and Narins 2002b -RRB- . The putative path for these vibrations includes the front limbs , the shoulder girdle and the m. opercularis -LRB- Hetherington 1988 ; Wever 1985 -RRB- . Alternatively , the operculum-columella system is proposed to protect the inner ear 's sensory organs from excessive stimuli . This protection hypothesis takes two different forms . Wever -LRB- 1985 -RRB- suggests that the operculum and the columella footplate can be locked together through muscle action . In this manner , the flexibility of the connection to the oval window decreases and the input impedance increases , which in turn decreases the input signal amplitude of the pressure wave in the inner ear . It has also been suggested that the action of the m. opercularis could uncouple the operculum and the footplate -LRB- Mason and Narins 2002b -RRB- . This would allow the operculum to move out of phase with the footplate . The out-of-phase motion could absorb part of the inner ear fluid displacement caused by the motion of the footplate . Effectively this creates an energetic by-pass and decreases the amplitude in the inner ear . A tympanic middle ear , as described above , is considered to be the typical situation -LRB- Jaslow et al. 1988 -RRB- , which can be found in the family Ranidae . However , a wide range of variations in middle ear structures is found across species . In some species , a bony disk occupies the tympanic annulus rather than a membrane , for example , Xenopus leavis -LRB- Wever 1985 -RRB- , and there are a number of `` earless '' frogs . The tympanic membrane and the tympanic annulus are absent in these species . A functioning inner ear and a partial middle ear usually exist , although the middle ear cavity may be filled with connective tissue -LRB- e.g. , Telmatobius exsul , Jaslow et al. 1988 -RRB- , or not exist at all -LRB- e.g. , species in the Bombina family , Hetherington and Lindquist 1999 ; Wever 1985 -RRB- . Remarkably , some of these `` earless '' frogs have a mating call and exhibit neurophysiological responses -LRB- Bombina bombina , Walkowiak 1988 ; Atelopus , Lindquist et al. 1998 -RRB- at typically auditory frequencies , which implies they have another path for the transfer of airborne sound to the inner ear -LRB- Jaslow et al. 1988 -RRB- , for example , through the lungs -LRB- Narins et al. 1988 ; Lindquist et al. 1998 ; Hetherington and Lindquist 1999 -RRB- . Inner ear The inner ear in the frog has two membranous windows : the oval window and the round window . As mentioned above , acoustic energy primarily enters the inner ear through the oval window . The round window is the main release point of this energy -LRB- Purgue and Narins 2000a -RRB- . A similar lay-out can be found in other terrestrial vertebrates . However , the round window of the frog does not open into the middle ear as it does in mammals . Rather , it can be found in the top of the mouth cavity , under a lining of muscle tissue . Within the inner ear , there are two intertwined membranous compartments : the perilymphatic and the endolymphatic labyrinths -LRB- see Fig. 1 -RRB- . The perilymphatic labyrinth connects to both the oval window and the round window . Starting at the oval window and going medially , it passes through a narrow foramen , and widens into the otic cavity , forming the periotic cistern . Continuing medially it narrows again into the periotic canal . This canal connects the periotic cistern with the perilymphatic space at the round window -LRB- Purgue and Narins 2000b -RRB- . Fig. 1Schematic drawing of a transverse section through the frog ear -LRB- adapted from Wever 1985 -RRB- . The division into the middle , and inner ear is indicated above the image ; a selection of features is indicated in the image . The colored arrows indicate the paths of vibrational energy : green arrows represent the columellar path , red arrows the putative opercular path , and blue arrows indicate the path through the inner ear after combination of the columellar and opercular paths . The grey areas represents endolympatic fluid , dark yellow perilymphatic fluid . The green areas indicate the tectorial membranes in the papillae . -LRB- Color figure is available in the online version -RRB- Between the lateral perilymphatic cistern and the round window , part of the endolymphatic space can be found . The endolymphatic space also includes the semi-circular canals located dorsally from the otic system . It contains the sensory organs of hearing and balance . In the frog inner ear , there are eight sensory epithelia -LRB- Lewis and Narins 1999 ; Lewis et al. 1985 -RRB- , located as follows : three cristae in the semi-circular canals , which are sensitive to rotational acceleration of the head , and one each in : the utricule , which detects linear acceleration , the lagena , which detects both linear acceleration and non-acoustic vibrations -LRB- Caston et al. 1977 -RRB- , the sacculus , which is sensitive substrate vibrations up to approximately 100 Hz , and also detects high level low-frequency airborne sound , -LRB- Narins 1990 ; Yu et al. 1991 -RRB- the amphibian papilla , which detects low-frequency acoustic stimuli -LRB- Feng et al. 1975 -RRB- , andthe basilar papilla , which is sensitive to high-frequency airborne stimuli -LRB- Feng et al. 1975 -RRB- . Hair cells are the sensory cells in all of these organs . Like all hair cells , these cells have a stereovillar bundle on their apical surface . Deflection of the bundle as a result of an acoustical vibration or a mechanical acceleration , initiates an ionic transduction current into the cell . This initial current causes a cascade of ionic currents , eventually resulting in the release of neurotransmitter at the basal surface of the cell . The released neurotransmitter triggers neural activity in the nerve fiber dendrites that innervate to the basal portion of the hair cell -LRB- Pickles 1988 ; Yost 2000 ; Keen and Hudspeth 2006 -RRB- . As in most vertebrates , a tectorial membrane covers the sensory cells of the auditory end organ . This membrane is a polyelectrolyte gel , which lies on the stereovilli -LRB- Freeman et al. 2003 -RRB- . The function of the tectorial membrane is not well understood , and may vary between classes . However , since the stereovilli in most vertebrate ears connect to this membrane , it obviously plays an important role in the conduction of acoustic vibrations to the hair cells . 3 Basilar papilla The basilar papilla is found in a recess that opens into the saccular space at one end , and is limited by a thin contact membrane at the other . The contact membrane separates the endolymphatic fluid in the papillar recess from the perilymphatic fluid at the round window -LRB- Lewis and Narins 1999 ; Wever 1985 -RRB- . The recess perimeter is roughly oval in shape ; in the bullfrog , Rana catesbeiana , its major axis is approximately 200 μm long , while the minor axis measures approximately 150 μm -LRB- Van Bergeijk 1957 -RRB- . In the leopard frog , Rana pipiens pipiens , it is of similar size -LRB- personal observation , RLMS & JMS -RRB- . The oval perimeter of the lumen is formed from limbic tissue ; a substance unique to the inner ear , and similar to cartilage -LRB- Wever 1985 -RRB- . The sensory epithelium is approximately 100 μm long . It occupies a curved area that is symmetrical in the major axis of the elliptical lumen . It contains approximately 60 hair cells -LRB- measured in Rana catesbeiana -RRB- , from which the stereovilli protrude into the lumen and connect to the tectorial membrane -LRB- Frishkopf and Flock 1974 -RRB- . Typically the orientation of the hair cells , as defined by the direction to which the v-shape of the stereovilli bundle points -LRB- Lewis et al. 1985 -RRB- , is away from the sacculus in Ranidae . The tectorial membrane spans the lumen of the papillar recess . It occludes about half the lumen , and consequently takes an approximately semi-circular shape when viewed from the saccular side -LRB- Frishkopf and Flock 1974 ; Wever 1985 -RRB- . The membrane has pores at the surface closest to the epithelium , into which the tips of the hair bundles project -LRB- Lewis and Narins 1999 -RRB- .4 Amphibian papilla The amphibian papilla can be found in a recess , that extends medially from the saccular space and , in frogs with derived ears , bends caudally to end at a contact membrane . Like the basilar papilla 's contact membrane , the membrane separates the endolymphatic fluid in the papilla recess from the perilymphatic fluid at the round window . The sensory epithelium is set on the dorsal surface of this recess -LRB- Lewis and Narins 1999 -RRB- . The epithelium itself has a complex shape ; it consists of a triangular patch at the rostral end , and an s-shaped caudal extension towards the contact membrane -LRB- see Fig. 2 -RRB- . The exact shape and length of the caudal extension varies across species , with the most elaborate extensions occurring in species of the family Ranidae -LRB- Lewis 1984 -RRB- , while some species lack the s-shaped extension altogether -LRB- Lewis 1981 -RRB- . Fig. 2Schematic drawing of the amphibian papilla of the bullfrog , Rana catesbeiana , -LRB- adapted from Lewis et al. 1982 -RRB- , rotated to match orientation of Fig. 1 -RRB- . TM Tectorial membrane , AP amphibian papilla . a General overview of the AP ; the dashed outline indicates the location of the sensory epithelium , b hair cell orientation in the sensory epithelium ; dashed line indicates the position of the tectorial curtain . The numbers along the perimeter indicate the characteristic frequency of the auditory nerve fibers connecting to that site -LRB- in Hz -RRB- In the epithelium , the hair cell orientation follows a complicated pattern -LRB- see Fig. 2b -RRB- . In the rostral patch the cells are orientated towards the sacculus . On the rostral half of the s-shaped extension , they are oriented along the s-shape . However , on the caudal half , the orientation rotates 90 ° to become perpendicular to the s-shape -LRB- Lewis 1981 -RRB- . An elaborate tectorial membrane is found on the hair bundles . A bulky structure covers the rostral patch , while the membrane gets thinner along the caudal extension -LRB- Lewis et al. 1982 -RRB- . A tectorial curtain spans the papilla recess approximately halfway between the sacculus and the contact membrane -LRB- Shofner and Feng 1983 ; Wever 1985 -RRB- . The curtain , also called the sensing membrane -LRB- Yano et al. 1990 -RRB- , spans the entire cross-section of the lumen . A small slit in the tectorial curtain may function as a shunt for static fluid pressure differences -LRB- Lewis et al. 1982 -RRB- . Response of the auditory end organs As mentioned in the section `` Anatomy '' , the oval window serves as the primary entry point of acoustic energy into the inner ear ; the round window presumably serves as the primary release point . After the energy passes through the oval window , it enters the periotic cistern . Between this relatively large perilymphatic space and the round window there are two possible routes : through the endolymphatic space , or through the periotic canal , bypassing the endolymphatic space and the sensory organs altogether -LRB- Purgue and Narins 2000a -RRB- . The bypass presumably serves to protect the sensory organs against low-frequency over stimulation -LRB- Purgue and Narins 2000b -RRB- . The vibrational energy that ultimately stimulates the auditory end organs predominantly may enter the endolymphatic space through a patch of thin membrane in its cranial wall near the sacculus . This entry-point was identified by Purgue and Narins -LRB- 2000b -RRB- , by mechanically probing the perimeter of the endolyphatic space . After entering the endolymphatic space , the energy may pass either through the basilar papilla 's or through the amphibian papilla 's lumen to the round window . Measurements of the motion of the respective contact membranes show that there is a frequency-dependent separation of the vibrational energy between paths through the amphibian and the basilar papilla -LRB- Purgue and Narins 2000a ; see Fig. 3c -RRB- . The accompagnying dynamic model of the energy flow through the bullfrog 's inner ear -LRB- Purgue and Narins 2000b -RRB- indicates that this separation may occur based on the acoustic impedances of the paths . Fig. 3Overview of measurements of the frog inner ear ; comparison between Rana -LRB- left -RRB- and Hyla -LRB- right -RRB- . The dashed lines indicate the separation between the amphibian papilla and the basilar papilla . a , b Distributions of characteristic frequencies of auditory nerve fibers in Rana pipiens pipiens , and Hyla cinerea . c Example of the response of the contact membrane in R. catesbeiana ; black line represents the amphibian papilla , open markers the basilar papilla . d , e Distributions of spontaneous otoacoustic emissions in ranid species -LRB- combined data from R. pipiens pipiens and R. esculenta -RRB- , and hylid species -LRB- combined data from H. cinerea , H. chrysoscelis , and H. versicolor -RRB- . f Example of stimulus frequency otoacoustic emissions in R. pipiens pipiens at indicated stimulus levels . g , h Examples of DP-grams measured in Rana pipiens pipiens , and Hyla cinerea . a , b , d , e , g and h are taken from Van Dijk and Meenderink -LRB- 2006 -RRB- . There they were reproduced from Ronken -LRB- 1990 -RRB- , Capranica and Moffat -LRB- 1983 -RRB- , Van Dijk et al. -LRB- 1989 , 1996 -RRB- , Meenderink and Van Dijk -LRB- 2004 -RRB- , and Van Dijk and Manley -LRB- 2001 -RRB- , respectively . c is taken from Purgue and Narins -LRB- 2000a -RRB- , and f is an adapted presentation of data from Meenderink and Narins -LRB- 2006 -RRB- -LRB- graph created with data provided by Dr. Meenderink -RRB- The perilymphatic path through the periotic canal may serve as a shunt for acoustical energy to the round window . As its impedance exponentially increases with frequency , low-frequency vibrations will most effectively utilize this path . The endolymphatic path , on the other hand , presumably has a relatively constant impedance throughout the frog 's auditory range . The respective lumina of the amphibian and basilar papilla have a frequency-dependent impedance of their own . According to the model mentioned above , these impedances are dominated by the characteristics of the contact membranes -LRB- Purgue and Narins -RRB- -LRB- 2000b -RRB- . The respective peak displacements of the contact membranes correspond to the detected frequencies in the associated organs -LRB- Purgue and Narins 2000a -RRB- . Basilar papilla The basilar papilla 's tectorial membrane is presumably driven by a vibrating pressure gradient between the the sacculus and the basilar papilla 's contact membrane . No reports have been published on direct measurements of the mechanical response of the tectorial membrane , or on the basilar papilla 's hair bundle mechanics . However , the hair cell orientation in the basilar papilla implies that the tectorial membrane 's primary mode of motion is to and from the sacculus . Auditory nerve fiber recordings from the frog basilar papilla show a frequency selective response -LRB- see Fig. 4 for examples of tuning curves -RRB- . The range of characteristic frequencies in nerve fibers from the basilar papilla is species dependent . In the leopard frog , they are approximately between 1,200 and 2,000 Hz -LRB- Ronken 1990 -RRB- ; in the bullfrog they are slightly lower , between 1,000 and 1,500 Hz -LRB- Shofner and Feng 1981 ; Ronken 1991 -RRB- . In the Hyla-family , the characteristic frequencies appear to be significantly higher ; in Hyla cinerea , the green treefrog , they range from 2.8 to 3.9 kHz -LRB- Ehret and Capranica 1980 ; Capranica and Moffat 1983 -RRB- , and in Hyla regilla roughly from 2 to 3 kHz -LRB- Stiebler and Narins 1990 ; Ronken 1991 -RRB- . Where studied in other species , the characteristic frequencies of the basilar papilla 's nerve fibers fall roughly within the bounds defined by the bullfrog at the low end and the green treefrog at the high end -LRB- Scaphiopus couchi : approximately 1 − 1.5 kHz , Capranica and Moffat 1975 ; Ronken 1991 ; Eleutherodactylus coqui : approximately 2 − 4 kHz , Narins and Capranica 1980 , 1976 ; Ronken 1991 ; Physalaemus pustulosus group : around 2.2 kHz , Wilczynski et al. 2001 -RRB- . Fig. 4Tuning curves measured in the auditory nerve in R. catesbeiana -LRB- unpublished measurements by JMS & PvD , 1992 ; various specimens -RRB- . The numbers in the graph indicate values In each individual frog , the tuning curves of the auditory nerve fibers appear to have a nearly identical shape and characteristic frequency -LRB- Ronken 1990 ; Van Dijk and Meenderink 2006 -RRB- . This suggests that the entire basilar papilla is tuned to the same frequency . Because of this collective tuning , characterized by one characteristic frequency and a single tuning-curve shape throughout the organ , the basilar papilla may be referred to as a `` single auditory filter '' . In comparison , the mammalian cochlea , and the anuran amphibian papilla -LRB- see below -RRB- , consist of a combination of a large number of auditory filters -LRB- Pickles 1988 -RRB- . The quality factor , Q10dB -LRB- e.g. , Narins and Capranica 1976 ; Shofner and Feng 1981 -RRB- , is lower than that of other vertebrate hearing organs in the same frequency range , -LRB- Evans 1975 ; see Fig. 5 -RRB- , and ranges from approximately 1 to 2 in both the leopard frog and the bullfrog -LRB- Ronken 1991 ; see Fig. 5 -RRB- . For other anuran species , the ranges are somewhat different , with the lowest minimum values -LRB- approximately 0.5 -RRB- reported for Hyla regilla , and the highest maximum values -LRB- approximately 2.8 -RRB- in Scaphiopus couchi . Thus , the basilar papilla 's frequency selectivity is relatively poor . Fig. 5Comparison of the filter quality factor versus the characteristic frequency -LRB- CF , in kHz -RRB- of nerve fibers from the cat cochlea -LRB- adapted from Evans 1975 -RRB- and the leopard frog -LRB- adapted from Ronken 1991 -RRB- . In the leopard frog graph , the triangular symbols correspond to nerve fibers from the amphibian papilla ; the circles to fibers from the basilar papilla . The black line indicates the upper limit of the amphibian papilla 's frequency domain . The grey area in the upper -LRB- cat -RRB- graph corresponds to the area of the lower -LRB- frog -RRB- graph . The loops indicate the approximate perimeter of the fiber populations in the lower graph for the amphibian papilla and the basilar papilla . As illustrated in Fig. 3 , there is no correspondence between the range of characteristic frequencies in the basilar papilla and the range of spontaneous otoacoustic emission frequencies -LRB- Van Dijk and Manley 2001 ; Van Dijk and Meenderink 2006 ; Van Dijk et al. 2003 ; Meenderink and Van Dijk 2004 , 2005 , 2006 ; Meenderink and Narins 2007 -RRB- . Since it is generally assumed that otoacoustic emissions of a particular frequency are generated at the detection site for this frequency , this suggests that the basilar papilla does not generate spontaneous emissions . However , it does emit distortion product otoacoustic emissions -LRB- Van Dijk and Manley 2001 -RRB- , and stimulus frequency otoacoustic emissions -LRB- Palmer and Wilson 1982 ; Meenderink and Narins 2006 -RRB- . The peak amplitudes of the distortion product otoacoustic emissions match the characteristic frequencies of the auditory nerve fibers innervating the basilar papilla -LRB- Meenderink et al. 2005 -RRB- . The amplitude and phase characteristics of the distortion product otoacoustic emissions can be qualitatively modeled by assuming the basilar papilla to be a single passive non-linear auditory filter -LRB- Meenderink et al. 2005 -RRB- . Thus , nerve fiber recordings , otoacoustic emission measurements and a model based on these measurements show that the basilar papilla functions as a single frequency band auditory receptor . This frequency band is relatively broad , and the center frequency may depend on species and individual animals . The hypothesis that considers the basilar papilla as a single resonator was originally put forward by -LRB- Van Bergeijk 1957 -RRB- . He investigated the mechanical response of the tectorial membrane in a scale model consisting of a thin rubber tectorium spanning a lumen in a stiff wall . A number of different vibration modes existed in this model . Although Van Bergeijk 's model is vastly oversimplified , the basic idea that the mechanical tuning of the tectorial membrane may be the basis of the basilar papilla 's frequency selectivity is still viable . Amphibian papilla As in the basilar papilla , the tectorial membrane in the amphibian papilla is presumably driven by a vibrating pressure difference between the sacculus and the round window . Due to the more elaborate tectorial membrane and the more complex pattern of hair cell orientations , the motion of the membrane may be expected to be more complex than that of the basilar papilla 's tectorial membrane . The tectorial curtain is in the sound path through the papilla , and presumably plays a role in conveying vibrations to the tectorial membrane and the hair bundles . Electrophysiological recordings from and subsequent dye-filling of single fibers of the auditory nerve show that the amphibian papilla has a tonotopic organization -LRB- Lewis et al. 1982 -RRB- . The fibers innervating the triangular patch have low characteristic frequencies , down to approximately 100 Hz . The frequencies increase gradually along the caudal extension . In the bullfrog , the upper frequency is about 1000 Hz ; an overview of the tonotopic organization is given in Fig. 2b . 5 The frequency selectivity of the amphibian papilla 's nerve fibers is similar to that of mammalian auditory nerve fibers with the same characteristic frequency . This is in contrast to the significantly poorer frequency selectivity in the basilar papilla 's nerve fibers -LRB- Ronken 1990 ; Evans 1975 ; see also Fig. 5 -RRB- . In the low-frequency , rostral part of the papilla , the hair cells are electrically tuned -LRB- Pitchford and Ashmore 1987 ; Smotherman and Narins 1999 -RRB- . This tuning stems from the electrical properties of the cell membrane 's ion channels . The hair cell tuning characteristics parallels the tonotopy of the single nerve recordings . Therefore , frequency selectivity in the rostral part of the amphibian papilla appears to be primarily determined by the electrical characteristics of the hair cells . However , there is a fundamental discrepancy between the tuning characteristics of the hair cells and the auditory nerve fibers . While hair cells exhibit a second-order resonance -LRB- Pitchford and Ashmore 1987 -RRB- auditory neurons display a higher order filter characteristic -LRB- Lewis 1984 -RRB- . Nevertheless , due to the parallels in the tonotopic organization , the assumption that the frequency selectivity is determined by the electrical tuning seems viable for the rostral part of the amphibian papilla . The higher-order responses in the neural signal may result from coupling between hair cells , which may be mechanical , for instance through the tectorial membrane . Neurons innervating the rostral portion of the amphibian papilla display non-linear two-tone suppression similar to that in other vertebrates -LRB- Capranica and Moffat 1980 ; Benedix et al. 1994 -RRB- . Another manifestation of non-linear behavior can be found in the response to noise : second-order Wiener kernels of low-frequency neurons show off-diagonal components , which are an indication of non-linearity -LRB- Van Dijk et al. 1994 , 1997 -RRB- . The spectro-temporal receptive fields constructed from these Wiener kernels exhibit suppressive side bands besides the main characteristic frequency band of the fiber -LRB- Lewis and Van Dijk 2004 -RRB- . Hair cells caudal to the tectorial curtain do not display electrical resonance -LRB- Smotherman and Narins 2000 -RRB- . Therefore , the tuning of this high-frequency , caudal region of the papilla must result from the mechanical properties of the tectorial membrane and the hair cells . Based on the hair cell orientation , displayed in Fig. 2b , the tectorial membrane motion in the amphibian papilla is expected to be far more complex than in the basilar papilla . Assuming that the hair bundles are orientated in such a way that they are maximally deflected by the connected tectorial membrane , the rostral patch of the membrane should be moving to and from the sacculus , if the appropriate stimuli are presented . The rostral part of the s-shaped extension is moving along its major axis , whereas the extension caudal to the tectorial curtain should be moving in a transverse direction . The amphibian papilla appears to be the only source of spontaneous otoacoustic emissions in the frog inner ear -LRB- Van Dijk et al. 1989 , 1996 ; Long et al. 1996 ; Van Dijk and Manley 2001 ; Fig. 3d-e -RRB- . The frequency distribution of these emissions corresponds to the range of best frequencies of the neurons projecting to the portion of the amphibian papilla caudal to the tectorial curtain . It is generally assumed that an otoacoustic emission of a specific frequency is generated at the location in the inner ear where that frequency is detected . Under this assumption , the presence of spontaneous otoacoustic emissions indicates that the caudal portion of the amphibian papilla exhibits spontaneous activity . Presumably , this activity is related to active amplification of input signals in this area . The caudal region of the amphibian papilla is also involved in the generation of distortion product otoacoustic emissions -LRB- Van Dijk and Manley 2001 ; Meenderink and Van Dijk 2004 -RRB- , and stimulus frequency otoacoustic emissions -LRB- Meenderink and Narins 2006 -RRB- . The distortion product otoacoustic emissions from the amphibian papilla are more vulnerable to metabolic injuries than those from the basilar papilla -LRB- Van Dijk et al. 2003 -RRB- . Also , both the spontaneous -LRB- Van Dijk et al. 1996 -RRB- and distortion product -LRB- Meenderink and Van Dijk 2006 -RRB- otoacoustic emissions display a clear dependence on body temperature . These results combine to indicate that the s-shaped extension of the amphibian papilla caudal to the tectorial curtain functions as an active hearing organ . Discussion Our aim in this review is to outline what is known about the mechanical response properties of the amphibian and basilar papilla . Only one published report exists of the direct mechanical measurements of structures associated with these papillae -LRB- Purgue and Narins 2000a -RRB- . The measurements show that the response of the contact membrane is frequency dependent for each papilla . The movement of the contact membrane may be assumed to reflect the fluid motion within the respective papilla . The contact membrane of the amphibian papilla shows a maximum response when the ear is stimulated with relatively low acoustic frequencies , while the basilar papilla contact membrane exhibits a maximum response to higher frequencies . The amphibian and the basilar papilla are the only hearing organs found in terrestrial vertebrates in which the hair cells are not on a flexible basilar membrane . Instead the hair cells are embedded in a relatively stiff cartilaginous support structure . Any frequency selective response , therefore , most likely originates from the mechanical or electrical properties of the hair cells , or the mechanical properties of the tectorial membrane , or a combination of these factors . Since there are no direct mechanical measurements of either the hair cells in the papillae or the tectorial membranes , we can not come to any definite conclusions regarding their properties . However , the available morphological and functional data allow for some hypotheses . The most conspicuous functional characteristic of the amphibian papilla is its tonotopic organization -LRB- Lewis et al. 1982 -RRB- . Rostral to the tectorial curtain , the hair-cell orientation is essentially parallel to the tonotopic axis . In this low-frequency region of the amphibian papilla , the tectorial membrane apparently moves in a rostro-caudal direction . In contrast , the hair-bundle orientation suggests that the tectorial-membrane motion is perpendicular to the tonotopic axis in the high-frequency , caudal region of the papilla . The tectorial membrane 's caudal end , therefore , appears to vibrate in a markedly different direction than its rostral end . In the low-frequency region of the amphibian papilla , the hair cells display electrical tuning . The tuning properties of the hair cells parallel the tonotopic organization are measured from the afferent nerve fibers -LRB- Pitchford and Ashmore 1987 -RRB- . This strongly suggests that the tuning characteristics of the nerve fibers are primarily determined by the electrical hair-cell resonances . The auditory nerve-fiber recordings reflect the presence of high-order filtering -LRB- Lewis 1984 -RRB- , whereas hair cells essentially function as second-order resonances . It is , therefore , likely that coupling between the hair cells shapes the frequency responses in the nerve fibers . Such coupling may be mechanical , for example , by the tectorial membrane , or electrical , or a combination of mechanical and electrical . Hair cells in the high-frequency , caudal region do not display any electrical resonance -LRB- Smotherman and Narins 1999 -RRB- . This implies that the frequency selectivity must be based on mechanical tuning , probably by the tectorial membrane . The caudal region of the amphibian papilla shares some notable characteristics with the mammalian cochlea -LRB- see also Lewis 1981 -RRB- : the papilla is elongated , and it exhibits a tonotopic gradient along the long axis ; the orientation of the hair cells is perpendicular to the tonotopic axis , indicating that the hair cells are stimulated most efficiently by a deflection perpendicular to the tonotopic axis ; frequency selectivity , very probably , relies on mechanical tuning ; frequency selectivity is similar , with Q10dB-values ranging from 0.8 to 2.2 ; andboth spontaneous and distortion product otoacoustic emissions are generated . These emissions are physiologically vulnerable . The presence of spontaneous otoacoustic emissions shows that at least part of the amphibian papilla 's caudal extension functions as an active hearing organ . In this respect it is similar to the mammalian cochlea and other vertebrate hearing organs -LRB- Lewis and Narins 1999 -RRB- . One active mechanism in the mammalian cochlea is the prestin-mediated active somatic length changes in the outer hair cells -LRB- Brownell et al. 1985 ; Yost 2000 ; Zheng et al. 2000 ; Liberman et al. 2002 ; Dallos 2003 -RRB- . However , this mechanism is probably exclusively present in mammalian outer hair cells . Active hair bundle movements have been reported as an alternative active mechanism in anuran saccular hair cells -LRB- Martin and Hudspeth 1999 ; Martin et al. 2003 ; Bozovic and Hudspeth 2003 -RRB- ; this mechanism may be present in the auditory organs as well . Although the fundamental active mechanism may differ between species , the functional result seems to be very similar across vertebrates : high auditory sensitivity and good frequency selectivity -LRB- Manley 2000 -RRB- . The basilar papilla seems to function in a much simpler manner . Both neural recordings and otoacoustic emission measurements suggest that it functions as a single auditory filter . Since the hair cells in the basilar papilla are unlikely to be electrically tuned , its frequency selectivity most likely results from mechanical tuning , probably via the tectorial membrane . The basilar papilla is remarkable in that no spontaneous otoacoustic emissions have been recorded in its frequency range . The absence of such emissions can either be caused by the fact that they are not generated within the papilla , or by the fact that the transmission of such emissions to the tympanic membrane is inhibited . However , distortion product otoacoustic emissions can be recorded in this range -LRB- e.g. , Van Dijk and Manley 2001 -RRB- . This implies that the outward transmission is not inhibited , and therefore that spontaneous emissions are most likely not generated within the basilar papilla . Furthermore , the amplitude of the basilar papilla 's distortion product otoacoustic emissions depends less on temperature than that of the amphibian papilla 's -LRB- Meenderink and Van Dijk 2006 -RRB- . Also , emissions from the basilar papilla are less sensitive to the disruption of oxygen supply -LRB- Van Dijk et al. 2003 -RRB- . Apparently , emissions from the basilar papilla are relatively independent of the metabolic rate , and therefore , it has been suggested that the basilar papilla is not an active hearing organ -LRB- Vassilakis et al. 2004 ; Van Dijk and Meenderink 2006 -RRB- . In conclusion , the frog inner ear takes an exceptional place among the hearing organs of terrestrial vertebrates . It includes two auditory end organs , which both lack the basilar membrane present in every other terrestrial vertebrate species . Instead the hair cells are embedded in a relatively stiff structure . They are stimulated by the motion of the tectorial membrane . Although the basilar and amphibian papilla are similar in this respect , they appear to function by different mechanisms . In fact , even within the amphibian papilla two distinctly different functional regions can be identified . The low-frequency portion , rostral to the tectorial curtain , contains hair cells that exhibit electrical tuning . The hair cells are most sensitive to deflection along the tonotopic axis , thus this is presumably the tectorial membrane 's direction of vibration . By contrast , the region caudal to the tectorial curtain shows more similarities to , for example , the mammalian cochlea : the hair cell orientation is perpendicular to the tonotopic axis , and the presence of spontaneous otoacoustic emissions suggests that it functions as an active hearing organ . Finally , the basilar papilla is yet different : it appears to function as a single passive auditory filter . Thus the frog inner ear includes two auditory end organs with three functional regions .

O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B I O O O O O O O O B B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B I O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B I I O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O

amphibian
anuran
frog
auditory system
inner ear mechanics


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

-LRB-

Fr

-RRB-

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

-LRB-

Hansen

Medical

Inc.

Mountain

View

CA

USA

-RRB-

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

-LRB-

Sensei

robotic

control

system

-RRB-

remote

catheter

manipulator

-LRB-

RCM

-RRB-

and

steerable

guide

catheter

-LRB-

Artisan

Control

Catheter

-RRB-

-LRB-

Fig.

-RRB-

Fig.

remote

catheter

manipulator

-LRB-

RCM

-RRB-

-LRB-

left

-RRB-

is

attached

to

the

steerable

guide

catheter

-LRB-

Artisan

-RRB-

through

which

a

mapping

catheter

can

be

positioned

within

the

heart

The

physician

's

workstation

-LRB-

right

-RRB-

navigates

the

steerable

guide

catheter

remotely

The

physician

's

workstation

The

physician

's

workstation

consists

of

display

screens

for

contact

intracardiac

electrophysiology

data

and

mapping

systems

as

well

as

a

central

fluoroscopic

control

view

also

displaying

a

superimposed

icon

of

the

Artisan

Control

Catheter

-LRB-

Fig.

-RRB-

Integral

to

the

workstation

and

its

control

of

the

Artisan

is

the

Instinctive

Motion

Controller

-LRB-

IMC

-RRB-

effectively

a

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

-LRB-

RCM

-RRB-

Fig.

Instinctive

Motion

Controller

-LRB-

top

left

-RRB-

used

with

a

control

panel

on

the

physician

's

workstation

-LRB-

bottom

left

-RRB-

remotely

guides

the

steerable

guide

catheter

which

can

be

seen

on

the

central

control

view

display

-LRB-

right

-RRB-

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

-LRB-

Artisan

-RRB-

The

Artisan

is

a

single

use

sterile

guide

catheter

that

is

composed

of

two

parts

a

steerable

inner

guide

within

a

steerable

outer

guide

-LRB-

Fig.

-RRB-

The

outer

guide

catheter

-LRB-

outer

size

Fr

inner

size

Fr

-RRB-

controlled

by

two

pull

wires

apart

provides

a

stable

base

for

the

inner

guide

-LRB-

Fr

outer

Fr

inner

-RRB-

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

and

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

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.

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

-LRB-

Table

-RRB-

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

and

exclusion

criteriaInclusion

criteriaExclusion

criteriaSuitable

for

catheter

mapping/ablationSevere

cerebrovascular

years

of

ageSerum

creatinine

Body

Mass

Index

gastrointestinal

bleedingSigned

informed

consentActive

infection

or

feverShort

life

expectancy

yearSignificant

anemiaSevere

electrolyte

imbalanceAllergy

to

contrastCongestive

heart

failure

-LRB-

NYHA

Class

IV

-RRB-

ejection

fraction

Unstable

angina

requiring

emergent

percutaneous

interventionRecent

myocardial

infarction

within

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

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

units

were

given

every

min

to

maintain

an

activated

clotting

time

of

at

least

s

The

Artisan

control

catheter

was

inserted

into

the

right

femoral

vein

through

a

short

non-irrigated

Fr

sheath

Various

conventional

and

mm

non-irrigated

tip

-LRB-

EPT

Blazer

II

-RRB-

and

irrigated-tip

-LRB-

Navistar

Thermocool

-RRB-

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

non-fluoroscopic

mapping

technologies

as

required

including

NavX

-LRB-

St.

Jude

Medical

St.

Paul

MN

USA

-RRB-

CARTO

and

CARTOMERGE

-LRB-

Biosense

Webster

Inc.

Diamond

Bar

CA

USA

-RRB-

All

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

Fr

venous

sheath

manually

If

heparin

had

been

given

during

the

procedure

intravenous

protamine

was

administered

and

removal

of

the

Fr

sheath

was

done

under

manual

pressure

once

the

activated

clotting

time

was

less

than

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

shows

the

procedures

undertaken

equipment

used

radiation

exposure

procedural

and

ablation

times

-LRB-

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

min

at

a

time

-RRB-

Figures

and

show

examples

of

the

use

of

the

steerable

catheter

in

combination

with

each

mapping

system

Fig.

of

the

use

of

the

remotely

controlled

catheter

sheath

in

conventional

electrophysiological

procedures

LAO

projection

of

a

left

free

wall

accessory

pathway

ablation

-LRB-

left

-RRB-

and

PA

projection

of

segmental

right

upper

pulmonary

vein

isolation

-LRB-

right

-RRB-

-LRB-

SGC

steerable

guide

catheter

Abl

ablation

catheter

tip

-RRB-

Fig.

mapping

system

images

created

using

the

remotely

controlled

steerable

guide

catheter

Anteroposterior

view

of

the

left

and

right

atrial

geometry

using

NavX

-LRB-

top

left

-RRB-

and

posteroanterior

view

of

the

left

atrium

during

wide

area

circumferential

ablation

using

CARTO

-LRB-

top

right

-RRB-

Posteroanterior

view

of

the

left

atrium

-LRB-

bottom

left

-RRB-

and

cross-sectional

view

of

the

left

sided

pulmonary

veins

-LRB-

bottom

right

-RRB-

during

segmental

pulmonary

vein

isolation

using

CARTOMERGE

-LRB-

Ablation

lesions

in

red

-RRB-

Table

ablation

procedural

dataPatientSexAgeDiagnosisProcedureMapping

systemCatheter

tipNumber

of

RFsRF

timeTotal

procedure

timeFlouro

timePatient

DAPWorkstation

mm

atrial

fibrillationPVI

left

atrial

mazeNavX

mm

atrial

fibrillationPVINavX

mm

pathwayPathway

mm

mm

atrial

fibrillationPVI

roof

line

MINavX

mm

atrial

fibrillationPVI

and

roof

lineNavX

mm

atrial

fibrillationPVI

and

roof

lineNavX

mm

ectopy/paroxysmal

atrial

fibrillationPVICARTOMERGE

mm

atrial

fibrillationPVI

and

roof

lineCARTO

mm

-LSB-

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

-LRB-

-RRB-

-RSB-

No

major

complication

occurred

One

patient

-LRB-

accessory

pathway

-RRB-

had

a

small

cm

pericardial

effusion

measured

on

echocardiogram

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

-LRB-

Mydose

Mini

X

Aloka

Co.

Ltd.

Japan

-RRB-

positioned

at

the

physician

's

workstation

approximately

m

away

from

the

X-ray

source

demonstrated

negligible

exposure

to

the

operator

despite

a

mean

cumulative

dose

area

product

of

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

-LSB-

-RSB-

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

-LSB-

-RSB-

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

-LSB-

-RSB-

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

-LRB-

mm

-RRB-

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

-LRB-

Fig.

-RRB-

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.

Intellisense

system

display

-LRB-

close-up

edited

view

-RRB-

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

-LRB-

from

white

to

yellow

-RRB-

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

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

-LSB-

-RSB-

Our

study

has

shown

that

negligible

operator

radiation

exposure

can

already

be

achieved

from

being

less

than

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

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

can

not

be

made

For

comparison

averaged

data

from

conventional

procedures

-LRB-

n

for

each

-RRB-

undertaken

at

our

laboratory

are

shown

in

Table

It

should

be

noted

that

this

data

represents

the

work

of

several

operators

of

varying

skill

and

experience

The

robotic

atrial

fibrillation

data

-LRB-

RF

time

min

procedure

time

min

n

-RRB-

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

ablation

procedural

dataAblation

procedureNumber

RFsRF

timeTotal

procedure

timeFlouro

timeDAPAtrial

fibrillation

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Atrial

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Accessory

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

-LRB-

-RRB-

Figures

represents

data

taken

from

conventional

procedures

-LRB-

n

-RRB-

for

each

arrhythmia

type

Means

are

given

with

standard

deviations

and

ranges

Times

are

in

minutes

RF

radiofrequency

energy

lesion

Dose

area

product

-LRB-

DAP

-RRB-

in

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

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

Below

is

the

link

to

the

electronic

supplementary

material

ESM

-LRB-

MOV

MB

-RRB-

O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

robotic navigation
catheter ablation
remote navigation