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Development of an AMR-ACB Array for Gastrointestinal Motility Studies Fabiano C. Paix˜ao, Luciana A. Cor´a, Madileine F. Am´erico, Ricardo Brandt de Oliveira, Oswaldo Baffa, and Jos´e Ricardo A. Miranda∗
Abstract—The association between anisotropic magnetoresistive (AMR) sensor and AC biosusceptometry (ACB) to evaluate gastrointestinal motility is presented. The AMR-ACB system was successfully characterized in a bench-top study, and in vivo results were compared with those obtained by means of simultaneous manometry. Both AMR-ACB and manometry techniques presented high temporal cross correlation between the two periodicals signals (R = 0.9 ± 0.1; P < 0.05). The contraction frequencies using AMR-ACB were 73.9 ± 7.6 mHz and using manometry were 73.8 ± 7.9 mHz during the baseline (r = 98, p < 0.05). The amplitude of contraction using AMR-ACB was 396 ± 108 μT·s and using manometry were 540 ± 198 mmHg·s during the baseline. The amplitudes of signals for AMR-ACB and manometric recordings were similarly increased to 86.4% and 89.3% by neostigmine, and also decreased to 27.2% and 21.4% by hyoscine butylbromide in all animals, respectively. The AMR-ACB array is nonexpensive, portable, and has high-spatiotemporal resolution to provide helpful information about gastrointestinal tract. Index Terms—Biomagnetics, biomedical equipment, biosusceptometry, gastroenterology, magnetoresistive device.
I. INTRODUCTION ETECTION and measurement of magnetic fields has significant technical, commercial importance, and a wide range of different detectors and systems have already been developed [1], [2]. With recent improvements in instrumental sensitivity and easiness of use as well as the growing interest from diverse areas, magnetic sensors have been recognized as valuable tools for biomedical and pharmaceutical applications [3]– [5]. Superconducting quantum interference device, anisotropic magnetoresistive (AMR), and AC biosusceptometry (ACB) are
D
Manuscript received March 13, 2012; revised June 11, 2012; accepted June 28, 2012. Date of publication July 13, 2012; date of current version September 14, 2012. This work was supported in part by the Fundac¸a˜ o de Amparo a` Pesquisa do Estado de S˜ao Paulo and the National Counsel of Technological and Scientific Development. F. C. Paix˜ao, L. A. Cor´a, and M. F. Am´erico had contributed equally to this work. Asterisk indicates corresponding author. F. C. Paix˜ao is with Universidade Estadual Paulista, Botucatu SP 010409010, Brazil (e-mail:
[email protected]). L. A. Cor´a is with the Universidade Estadual de Ciˆencias da Sa´ude de Alagoas, Macei´o, AL 57010-300 Brazil (e-mail:
[email protected]). M. F. Am´erico is with the Universidade Federal de Mato Grosso, Barra do Garc¸as, MT 78060-900 Brazil (e-mail:
[email protected]). R. B. de Oliveira and O. Baffa are with the Universidade de S˜ao Paulo, Ribeir˜ao Preto SP 14015-000, Brazil (e-mail:
[email protected];
[email protected]). ∗ J. R. A. Miranda is with the Universidade Estadual Paulista, Botucatu SP 010409-010, Brazil (e-mail:
[email protected]). Digital Object Identifier 10.1109/TBME.2012.2208748
noninvasive and radiation-free sensors currently available for such purposes. AMR sensors are based on the anisotropic magnetoresistance effect and are available for a wide range of applications [6], [7]. Most of these sensors are made of a nickel–iron (permalloy) thin film deposited onto a silicon substrate and is patterned as a resistive strip [8], [9]. Their principle of operation is based on the electrical resistance of the film which can be modulated by the application of a magnetic field in the direction of its inherent magnetization [6], [10]. ACB sensors employ induction coils to measure biomagnetic fields resulting from ferromagnetic sources in response to an applied ac magnetic field [11], [12]. These sensors are composed of pairs of detection and excitation coils in a first-order gradiometric configuration to provide good signal-to-noise ratio. Considering their features, AMR sensors can detect constant and time-varying magnetic fields [7], [13], [14], while ACB sensors are able to measure alternating magnetic field and to monitor ferromagnetic particles that were not previously magnetized [5], [11], [12]. The association between AMR and ACB consists of replacing the ACB detection coils by AMR sensors. The idea was to combine the spatial resolution of the AMR with the convenience of ac excitation [3], [15]. The gastrointestinal (GI) motor activity represents a multifaceted and complex group of functions that are essential for life [16], [17]. Several methods are available for assessment of the gastric contractions in humans and animals, but are limited by ionizing radiation, spatial resolution, invasiveness, and cost [18]. In the process of validating the ACB technique, magnetic data showed accuracy and close agreement with standard techniques in humans and dogs [19]–[22]. The aims of this study were to develop, to characterize the performance of an AMR-ACB array, and to determine the accuracy of this device to evaluate gastric motor activity in dogs, using manometry as the comparative method. II. METHODS A. AMR AMR sensors consist of a hard axis with a high requirement of magnetization energy in one direction in the plane of the film and orthogonal to the hard axis, which indicates the magnetic preference direction. The resistance of the thin film varies with the direction of the magnetization [8], [10]. The direction of magnetization is determined by several factors including the anisotropy axis, which is defined by the magnetic field present during the deposition of the film and the shape of the film.
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The magnetization m has preferential direction of the magnetic field applied, the resistance R of the thin film varies according to the magnetization, and consequently, it is highest when the magnetization is parallel to the current I and lowest when it is perpendicular. Changing the magnetization from an initial state consistent with anisotropy axis, through the application of an external field Hx in the film plane, causes the maximal resistivity change. The resistance change Rx making an angle ε with the anisotropy axis described as 1 h2x cos 2ε + hx 1 − h2x sin 2ε − cos 2ε . 2 (1) By definition, hx is the relative value of magnetic field perpendicular to anisotropy axis and ΔRm is the maximum change of resistance [8]. Basically, AMR sensors detect the field hx in the film plane as a result of the difference of the resistance. In the case of measured field making an angle y with the sensor axis, the output signal should be proportional to the component of this field Hx cos y. AMR sensors detect magnetic field varying between 100 pT and 100 mT [23]. The main properties of AMR sensors are their sensitivity at weak magnetic fields, dimensions of the film, linearity, and resolution. The sensitivity increases with diminishing film thickness [6]–[8], [23]. It can be assumed in practical design that for a fixed thickness t and width w, there is an optimum value t/w; thus, the sensitivity increases with decreasing t/w ratio. Regarding the linearity, anisotropy values vary markedly in the film due to the nonuniformity in the demagnetizing field and, also, due to the magnetization direction that is variable into film with nonzero angle between the path and the anisotropy axis. For the resolution, it can be assumed that this parameter is limited for small output signal values by amplifier noise and it can be improved by introduction of an ac supply [6]–[10]. ΔRx ≈ ΔRm
B. ACB ACB sensors are composed of two pairs of coils separated by a fixed distance (baseline), where each pair of coils is constituted by an excitation coil (outer) and a detection coil (inner), in a first-order gradiometric configuration (see Fig. 1). This system is based on a pair of magnetic flux transformers with air nucleus where the pair (excitation/detection) located far from the magnetic source works as the reference, while the pair closer to the sample is the measure transformer [11], [12], [24]. The excitation coil operates with a frequency of 10 kHz to provide low offset and high sensitivity as well as to avoid significant eddy current effects produced by biological tissue in the presence of the electrically conductive fluids. In this system, a current of 15 mA is needed to generate a magnetic field of 2 mT (measured in the center of excitation coil) which induces magnetic flux in the detection coils [5]. ACB sensors detect magnetic fields around 10 μT. Hence, the output voltage Vd is the result from the difference of inductance ΔM for the two pair of coils in relation to the currents supplied to the excitation coils Ie , and to the amplifier in the measurement
Fig. 1. Schematic diagram of the ACB system. Detection, 1, and excitation, 2, coils are coaxially arranged. Ideally when no magnetic material is close to this arrangement, the current Ie in the excitation coils generates a voltage in each coil that is canceled by the gradiometric configuration. Only the signal from the ferromagnetic source coupled to the coil is detected as the difference of inductance M. (Modified from [5].)
Fig. 2. Diagram of AMR-ACB array showing the detectors, 1–4 and the reference sensor, 5. Layout of the electronic chain representing only one sensor.
system I as also the electrical resistance R in the detection coils Vd = ΔM
dIe + RI. dt
(2)
C. AMR-ACB 1) Instrumentation: The AMR-ACB array was built on a nylon support and consisted of two excitation coils separated by a baseline of 100 mm (see Fig. 2). The excitation coils were made with 220 turns, 26-AWG wire, and 55-mm internal diameter. AMR sensors (HMC1001, Honeywell Inc., Morristown, NJ), one-axis sensing, ±2 Gauss field range, and 3.2 mV/V/Gauss sensitivity and set/reset pulse circuit were used [3], [15]. Four AMR sensors were set in the inner part of the plane containing the excitation coil with a distance of 15 mm among them, according to the radial symmetry of the magnetic field produced by the coil. This arrangement was designed as detection system. The reference system consisted of one AMR sensor placed in the center of the other excitation coil. The excitation coils were utilized to produce an ac magnetic field of 10 kHz supplied by a lock-in amplifier (SR-830 DSP,
˜ et al.: DEVELOPMENT OF AN AMR-ACB ARRAY FOR GASTROINTESTINAL MOTILITY STUDIES PAIXAO
Stanford Research System, Sunnyvale, CA) connected directly to the power amplifier. AMR sensors were employed to measure the magnetic field variation obtained from the response of the ferromagnetic material when an alternating magnetic field was applied on the ferromagnetic sample. Since AMR-ACB signal detection depends on the distance between the sensor and the magnetic material, changes in their relative position during gastric contraction and relaxation can modulate the signal recorded by the sensor. The gradiometric output signal from sensors was preamplified and detected by lock-in amplifiers to provide dc output in four positions. The signals were connected to the personal computer using an analog-to-digital board (PCI-MIO-16XE-10, National Instruments Inc., Austin, TX). The signal acquisition was made in LabView (National Instruments Inc.) and postprocessed using computational routines in MATLAB (The MathWorks Inc., Natick, MA). 2) Theoretical Model: The detector and reference sensors are enclosed by two identical pickup coils wound in the same direction with radius a, number of turns N, and carried with the same current intensity I = I0 sin(wt). The distance from the sample to each central sensor is r1 –r5 , and the separation between the detector and reference sensor and excitation coils is b, such that r5 = r1 + b. The amplitude of the excitation field produced at the sample BE T is the sum of the amplitude of the field generated by two coils, i.e., BE T = B1 + B2 ; then, the amplitude of the excitation field can be expressed as a2 μ0 N I a2 BE T = rˆ (3) 3/ + 3/ 2 (r2 + a2 ) 2 (r2 + a2 ) 2 1
5
where μ0 is the vacuum permeability. The magnetization induced at the sample produce a magnetic field that will be given by M = χm BE T /μ0 , where χm is the magnetic susceptibility. The total field measured by detector 1 will be BD 1 = B1 + B2 + M + BN , where BN is the magnetic environmental noise. For detector 5, the field measured will be BD 5 = B1 + B2 + BN , considering the sample far from the detector 5. Assuming the sample as a magnetic marker and its response from the magnetic field excitation as a single coil of radius d, the resulting signal for a differential combination of detectors 1 and 5 will be given by a2 μ0 χm N I a2 BD (1−5) = 3/ + 3/ 4 (r12 + a2 ) 2 (r52 + a2 ) 2 d2 × rˆ. (4) 3/ (r12 + d2 ) 2 The voltage produced by the gradiometric array will be linear proportional to these fields through a calibration constant. Thus, the voltage produced at sensor 1 is VD 1 = αBD (1−5) . Then, if there is no sample near to the detector, the output is VD 1 = 0. The same analysis can be applied to the other possible combinations of sensors, 2–5, 3–5, and 4–5, assuming that the exciting magnetic field is the same for all the sensors. The difference between magnetic excitation due the position of detectors 2, 3,
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and 4 inside the coil is balanced with an offset voltage in the differential amplifier. Since the magnetic signal depends on the distance between the sensor positioned on the abdominal surface and the ingested magnetic material, the movements of the GI wall generated by smooth muscle contractions promote direct modulations in the signal representing stomach motility. These modulations in the signal characterize the gastric motor activity, which can be monitored by AMR sensors in four distinct points. D. AMR-ACB Characterization Characterization of AMR-ACB array was performed in order to obtain the profile of the dependence of the magnetic field at different distances. In bench-top tests, a magnetic tablet was used. The tablet was obtained by direct compression of 1.00 g of ferrite powder (MnFe2 04 ; 80 ≤ φ ≤ 125 μm) mixed with 0.52 g of microcrystalline cellulose (Merck, Germany). The tablet has a cylindrical form weighing 1.52 g, with 10 mm of diameter, 7 mm of length, and a density of 2.03 g/cm3 . For axial sensitivity tests, the magnetic marker was aligned with the detection axis of the AMR-ACB array, and then, it was moved at fixed distances from 0 to 60 mm. The same test was repeated by employing conventional ACB device. For transversal sensitivity tests, the magnetic marker was moved perpendicularly to the excitation axis of AMR-ACB array at fixed distances (15 mm) from 0 to 80 mm, and this procedure was repeated by employing conventional ACB device. Both tests were performed in order to compare the results regarding sensitivity properties from AMR-ACB array and conventional ACB system. In order to establish a correlation between the signals from AMR-ACB and manometry, the following in vitro experiment was made. A balloon was filled with 35 ml of yogurt containing 4.00 g of ferrite powder and then connected to a pressure transducer (MP100 System; Biopac Inc., Santa Barbara, CA). The AMR-ACB sensor was positioned over the balloon at a fixed distance. A glass arch was rolled at 1-mm intervals (1–12 mm) on the balloon to simulate contraction rings, and to establish an amplitude relationship between the AMR-ACB and manometry. E. Animal Testing Magnetic and manometric measurements have been performed simultaneously. Eight healthy beagle dogs (8–14 kg) were used in the study. All experimental procedures were carried out in accordance with the American Physiological Society’s Guiding Principles in the Care and Use of Animals and were approved by the local Animal Ethics Committee. All animals were anesthetized (pentobarbital, 30 mg.kg−1 ) and kept supine in a gutter-type table. The manometry catheter with a balloon at the probe tip was introduced through the mouth into the stomach. Once positioned inside the stomach, the balloon was filled with 35 ml of yogurt containing 4.00 g of ferrite powder, and then connected to a pressure transducer (MP100 System; Biopac Inc., Santa Barbara, CA) for intragastric pressure monitoring [25].
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Fig. 3. Diagram showing the positioning of manometry catheter with a balloon at the end (dashed) and of AMR-ACB array (circles) on the abdominal surface of the dog.
The AMR-ACB array was fixed in an articulated apparatus to be positioned on the canine abdominal surface. The sensor located at the center of the array (sensor 1) was positioned at the point of maximum magnetic field intensity (see Fig. 3). Respiration was monitored simultaneously through a thermocouple sensor positioned in the dog’s nostril. Simultaneous magnetic and manometric continuous recordings were obtained for 30 min; at the end of the 10th min neostigmine methylsulfate (Prostigmine, Roche, Madrid, Spain) 0.04 μg/Kg was administered intravenously, and 10 min later 2.2 mg/Kg of hyoscine n-butylbromide (Buscopan, Boehringer Ingelheim, Germany) was given intravenously. F. Data Analysis All raw signals were analyzed in MATLAB (The Mathworks, Inc., Natick, MA) by visual inspection and by using bidirectional Butterworth bandpass filters by fast Fourier transform first and then by running spectrum analysis [26]. Temporal cross correlation R analysis was used to determine the correlation between recordings obtained from AMR-ACB and manometry. Nonparametric Spearman rank correlation test r was used to determine the correlation between AMR-ACB and manometry frequencies of contraction. Area under contraction was calculated by employing the same filters described previously. A comparison of all evaluated periods has been performed for both magnetic and manometric techniques. The inhibitory time (after hyoscine n-butylbromide administration) was defined as the time when the intensity of gastric activity contraction returned to at least 75% of baseline values. The statistical significance of differences between AMRACB and manometry considering signal amplitudes and frequencies before and after drugs was determined with the paired student’s t-test. Differences were considered statistically significant at P ≤ 0.05. The data are presented as mean ± SD (standard deviation).
Fig. 4. Variation of magnetic field detected as function of the (a) axial and (b) radial displacement of magnetic marker. For the transversal displacement the marker was positioned at 15 mm from the detection coil. Open squares represent the conventional ACB, closed circles represent the central AMR, open triangles represent the lateral AMR, and closed triangles represent the theoretical model.
III. RESULTS AND DISCUSSION Fig. 4 represents the axial and transversal sensitivity profiles obtained for both AMR-ACB array and conventional ACB system employing a magnetic marker. Fig. 4(a) shows the dependence of the signal intensity with axial distance for the AMR sensors 1 and 2, as well as ACB and the simulation of theoretical model (4). AMR-ACB array has lower sensitivity and, consequently, its dependence of the distance to the magnetic material is higher than that obtained for conventional ACB system. For the interval between 0 and 2.5 cm, the magnetic field measured by the AMR-ACB array decays −2.4, while the signal measured by conventional ACB system decays −1.5. For the interval between 2.5 and 6.0 cm, the magnetic field measured by the AMR-ACB array and conventional ACB system decays −4.9 and −4.4, respectively. The ACB with coil and AMR sensor have different geometries. The detector coil for the ACB measures the change in magnetic flux in a relatively large area determined by the diameter of the coil, and the AMR sensor measures the magnetic
˜ et al.: DEVELOPMENT OF AN AMR-ACB ARRAY FOR GASTROINTESTINAL MOTILITY STUDIES PAIXAO
Fig. 5. In vitro correlation between AMR-ACB and manometry amplitude values. The equation of the straight line showed a strong positive correlation between techniques and demonstrating the sensitivity of the magnetic method.
field in a smallest area. The AMR-ACB’s theoretical model was simplified and it assumed the magnetic field on the axis and replaced the magnetic marker by coil. This hypothesis holds only for certain distances and it is strongly dependent on the relative dimensions of the source and sensor, and these influences can be seen in Fig. 4(a). The theoretical model considers that the excitation on the sample and the dipolar source was homogenous. In fact, these are the main factors which provided the differences between the theoretical and experimental curves. Fig. 4(b) shows that the spatial resolution obtained for AMRACB array is higher than that obtained with the ACB conventional. For AMR-ACB, the spatial resolution was evaluated as the inverse at half-width which was measured by sensors located centrally and laterally in the array was 0.043 and 0.029 mm−1 , respectively. For ACB conventional, the same parameter measured was 0.017 mm−1 . Hence, it was possible to conclude that despite the lower AMR-ACB array sensitivity, its spatial resolution is much better than that of conventional ACB. These results ensure greater precision to locate the magnetic material within the organs. A strong linear correlation (R = 0.997) was observed in amplitude between AMR-ACB and manometric recordings in vitro. Small variations in the signal amplitudes generated equal positive responses from AMR-ACB and manometry (see Fig. 5). In vitro experiments demonstrated the high sensitivity of the AMR-ACB method for measuring modulations similar those caused by the GI contractions. Our study was based on signals from magnetic material inside of balloon surrounded by gastric wall, and their movements promoted by contractions are detected by AMR-ACB since the online magnetization is continuous and always in one direction. To establish AMR-ACB as a reliable technique for recording the contractile activities of the GI tract, definitive validation required an invasive approach. The AMR-ACB array was employed to record the GI motility in dogs and data were comparable with manometry. Fig. 6 illustrates AMR-ACB and manometric recordings from distal stomach in an anesthetized
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Fig. 6. Typical effects of neostigmine (arrow) and hyoscine butylbromide (headarrow) on signals and RSA from AMR-ACB and manometry recorded simultaneously in the stomach.
TABLE I EFFECTS OF NEOSTIGMINE AND HYOSCINE BUTYLBROMIDE ON AMPLITUDE AND FREQUENCY OF THE SIGNALS RECORDED BY AMR-ACB AND MANOMETRY
animal, showing that the changes caused by drugs were contemporary in both recordings. In addition, the spectral analysis of AMR-ACB and manometry recordings from the stomach reveals that both periodic signals occurred within the same frequency range. AMR-ACB and manometry presented a high correlation at gastric frequency (see Table I) and the changes caused by neostigmine (decrease) and hyoscine (increase) in AMR-ACB signal frequency were parallel to those seen in manometric recordings. The frequency spectra of the periodic signals recorded simultaneously by AMR-ACB and manometry were virtually identical (see Fig. 6 and Table I), and correspond to the well-known narrow frequency spectrum of the canine gastric activity [27], [28]. The amplitude of contraction using AMR-ACB was 396 ± 108 μT·s and using manometry was 540 ± 198 mmHg·s during the baseline. The amplitudes of signals for AMR-ACB and manometric recordings were similarly increased to 86.4% and 89.3% by neostigmine, and also decreased to 27.2% and 21.4% by hyoscine butylbromide in all animals, respectively (see Table I). The inhibitory effect of hyoscine butylbromide on
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contraction intensity lasted for 8.5 ± 0.5 min when detected by AMR-ACB and 8.7 ± 0.6 min when detected by manometry. Both AMR-ACB and manometry techniques also presented high temporal cross correlation between the two periodicals signals (R = 0.9 ± 0.1; P < 0.05). In this study, the striking similarities between results of AMR-ACB and manometry, a direct indicator of GI mechanical activity, provide validation for AMR-ACB as method for assessment of GI contractile activity in vivo. The effects of both drugs are expected, but our results showed that AMR-ACB is a reliable tool to investigate these effects on gastric activity contraction. Several methods are used to evaluate frequency of contractions in research, but their implementation in the clinical practice is still restricted to few groups of patients [29]. Moreover, several drugs can affect frequency of contractions and new data could offer additional insights into normal physiology and the alterations caused by them. The main advantage of the AMR-ACB system is its spatial resolution, since it allows monitoring more specific point focusing on frequency and amplitude variations, especially considering experimental animals regularly used such as rats and mice. Additionally, the largest advantage is the use of AMR-ACB through the magnetic material ingestion without any surgery or catheter introduction. AMR-ACB does not depend on the excitation frequency, while in the conventional ACB, the response is directly dependent on the excitation frequency. This approach increases the signal-to-noise ratio because it minimizes the eddy current from the tissues, minimizing the breath effects.
IV. CONCLUSION Our data showed that signals from AMR-ACB presented a good temporal correlation with manometry, and this system was able to track any frequency change of the gastric activity. The advantages offered by this novel sensor arrangement include the lack of previous meal magnetization and the possibility to evaluate continuously the GI motility as well as pharmaceutical processes. New insights about gastric abnormalities, appropriate animal models, and recording tools could be interesting for both physiological and clinical applications. In this context, a portable, low cost, and high-spatiotemporal-resolution AMR-ACB array was successfully implemented and validated for recording of gastric activity contraction as well as the influence of drugs on this parameter. AMR-ACB array has hybrid characteristic since that can be used with excitation coils or without them, after magnetization of the meal. Latest technical developments of 3-D AMR sensors will provide more reliable information about motility by measuring the magnetic field vector instead of only the axial component.
ACKNOWLEDGMENT The authors would like to thank Dr. M. Stelzer and R. Moraes for their technical support.
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˜ et al.: DEVELOPMENT OF AN AMR-ACB ARRAY FOR GASTROINTESTINAL MOTILITY STUDIES PAIXAO
[24] L. A. Cor´a, M. F. Am´erico, F. G. Romeiro, R. B. Oliveira, and J. R. A. Miranda, “Pharmaceutical applications of AC Biosusceptometry,” Eur. J. Pharm. Biopharm., vol. 74, no. 1, pp. 67–77, 2010. [25] R. Moraes, L. Cor´a, M. Am´erico, R. Oliveira, O. Baffa, and J. Miranda, “Measurement of gastric contraction activity in dogs by means of AC biosusceptometry,” Physiol. Meas., vol. 24, pp. 337–345, 2003. [26] S. N. Reddy, S. M. Collins, and E. E. Daniel, “Frequency analysis of gut EMG,” Crit. Rev. Biomed. Eng., vol. 15, no. 2, pp. 95–116, 1987. [27] J. Xing, L. Qian, and J. Chen, “Experimental gastric dysrhythmias and its correlation with in vivo gastric muscle contractions,” World J. Gastroenterol., vol. 12, no. 25, pp. 3994–3998, Jul. 2006. [28] W. J. Lammers, L. Ver Donck, B. Stephen, D. Smets, and J. A. Schuurkes, “Origin and propagation of the slow wave in the canine stomach: the outlines of a gastric conduction system,” Amer. J. Physiol., vol. 296, no. 6, pp. G1200–G1210, May 2009. [29] S. Muller-Lissner, G. N. Tytgat, L. G. Paulo, E. M. Quigley, J. Bubeck, H. Peil, and E. Schaefer, “Placebo- and paracetamol-controlled study on the efficacy and tolerability of hyoscine butylbromide in the treatment of patients with recurrent crampy abdominal pain,” Aliment. Pharmacol. Ther., vol. 23, pp. 1741–1748, 2006. Fabiano C. Paix˜ao received the Graduate degree in physics and the Ph.D. degree in general and applied biology from the Universidade Estadual Paulista (UNESP), Botucatu, Brazil, in 2004 and 2009, respectively. In 2008, he participated in research at the Gastrointestinal SQUID Technology Laboratory, Vanderbilt University Nashville, TN. In 2010 and 2011 early, he was an Adjunct Professor at the Pontifical Catholic University of Rio Grande do Sul and former Professor in the Department of Physics and Biophysics, UNESP, between 2006 and 2009. He is currently a Postdoctoral Fellow in the Biomag Research Lab at the UNESP. His current interests include biomedical instrumentation, modeling biological processes, gastrointestinal motility, magnetic image, and biomagnetism.
Luciana A. Cor´a received the Graduate degree in biomedicine, and the M.S. and Ph.D. degrees in pharmacology from the Sao Paulo State University, Botucatu, Brazil, in 2001, 2004, and 2008, respectively. From 2009 to 2010, she was a Postdoctoral Fellow at the University of Sao Paulo. She is currently an Associate Researcher at the Alagoas University of Health Sciences, Macei´o, Brazil. Since 1999, she has been involved in research on gastrointestinal tract, and has gained considerable expertise in the areas of pharmacy, signal and image analysis, biomagnetism, and biomedical instrumentation.
Madileine F. Am´erico received the Graduate degree in biomedicine from the Sao Paulo State University, Botucatu, Brazil, in 2001, and the M.S. and Ph.D. degrees in physiology from the University of Sao Paulo, Ribeir˜ao Preto, Brazil, in 2003 and 2008, respectively. From 2009 to 2010, she was a Postdoctoral Fellow at the Sao Paulo State University. Since 2010, she has been researching and teaching as an Associate Professor at the University Federal of Mato Grosso, Barra do Garc¸as, Brazil. Since 1999, she has been involved in research on gastrointestinal tract, and has gained considerable expertise in the areas of physiology, sensor signal analysis, electrophysiology, and biomagnetism. Her current research interests include several aspects of gastrointestinal motility in laboratory animals.
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Ricardo Brandt de Oliveira received the M.D. and Doctor of Medical Sciences degrees from the University of Sao Paulo, Ribeir˜ao Preto, Brazil, in 1970 and 1978, respectively. In 1983, he was a Postdoctoral Researcher at the Welsh National School of Medicine, U.K. Since 1974, he has been a Distinguished Professor in the Department of Internal Medicine, University of Sao Paulo. He is the author or coauthor of more than 140 peer-reviewed research papers related to gastrointestinal tract and several book chapters. He obtained a research productivity grant from the National Counsel of Technological and Scientific Development, Brazil. His research interests include several aspects of the gastrointestinal tract addressing clinical, biopharmaceutical, and pathophysiology investigations.
Oswaldo Baffa received the B.Sc. degree in physics from the Instituto de F´ısica e Qu´ımica de S˜ao Carlos, University of Sao Paulo, Ribeir˜ao Preto, Brazil, in 1976, where he also received the Master’s and Doctoral degrees, both in applied physics (molecular biophysics), in 1980 and 1984, respectively. Since then, he has worked in interdisciplinary projects in the biophysics/medical physics interface. In 1981, he joined the Departamento de F´ısica, Faculdade de Filosofia, Ciˆencias e Letras de Ribeir˜ao Preto, Universidade de S˜ao Paulo, as an Assistant Professor, where he was promoted to a Professor in 1996. A postdoctoral internship (during 1986–1988) at the Department of Medical Physics, University of Wisconsin-Madison (UW-Madison), was influential in the establishment of a research group in biomagnetism that gained national and international recognition. He has maintained a long-standing collaboration with the Biomagnetism Research Laboratory at the UW-Madison Department of Medical Physics, where he is currently a Visiting Professor. His early career interests were mainly in the field of biophysics, medical physics, biomagnetic, electron spin resonance for dosimetry and dating, magnetic resonance imaging, magnetic resonance spectroscopy, and functional magnetic resonance imaging. He has contributed to more than 150 scientific papers and patents with several collaborators in Brazil and abroad. Prof. Baffa is an Associate Researcher at the Brazilian National Research Council (CNPq).
Jos´e Ricardo A. Miranda received the Graduate degree in physics from the Federal University of Sao Carlos, Sao Carlos, Brazil, in 1986, and the M.S. and Ph.D. degrees in physics applied to medicine and biology from the University of Sao Paulo, Ribeirao Preto, Brazil, in 1991 and 1995, respectively. Since 1994, he has been researching and teaching as a Professor in the Department of Physics and biophysics, Universidade Estadual Paulista, Botucatu, Brazil. He is an author or coauthor of several peerreviewed research papers related to applications of biomagnetism on gastrointestinal tract. He obtained a research productivity grant from the National Counsel of Technological and Scientific Development, Brazil. His current interests include digital signal and image processing, biomedical instrumentation, biomagnetism, electrophysiology, gastrointestinal motility, and drug delivery.
