Noninvasive biomagnetic detection of intestinal slow wave dysrhythmias in chronic mesenteric ischemia.

Chronic mesenteric ischemia (CMI) is a challenging clinical problem that is difficult to diagnose noninvasively. Diagnosis early in the disease process would enable life-saving early surgical intervention. Previous studies established that superconducting quantum interference device (SQUID) magnetometers detect the slow wave changes in the magnetoenterogram (MENG) noninvasively following induction of mesenteric ischemia in animal models. The purpose of this study was to assess functional physiological changes in the intestinal slow wave MENG of patients with chronic mesenteric ischemia. Pre- and postoperative studies were conducted on CMI patients using MENG and intraoperative recordings using invasive serosal electromyograms (EMG). Our preoperative MENG recordings showed that patients with CMI exhibited a significant decrease in intestinal slow wave frequency from 8.9 ± 0.3 cpm preprandial to 7.4 ± 0.1 cpm postprandial (P < 0.01) that was not observed in postoperative recordings (9.3 ± 0.2 cpm preprandial and 9.4 ± 0.4 cpm postprandial, P = 0.86). Intraoperative recording detected multiple frequencies from the ischemic portion of jejunum before revascularization, whereas normal serosal intestinal slow wave frequencies were observed after revascularization. The preoperative MENG data also showed signals with multiple frequencies suggestive of uncoupling and intestinal ischemia similar to intraoperative serosal EMG. Our results showed that multichannel MENG can identify intestinal slow wave dysrhythmias in CMI patients.

Biomagnetic characterization of spatiotemporal parameters of the gastric slow wave.

Certain gastric disorders affect spatiotemporal parameters of the gastric slow wave. Whereas the electrogastrogram (EGG) evaluates electric potentials to determine primarily temporal parameters, fundamental physical limitations imposed by the volume conduction properties of the abdomen suggest the evaluation of gastric magnetic fields. We used a multichannel superconducting quantum interference device magnetometer to study the magnetogastrogram (MGG) in 20 normal human subjects before and after a test meal. We computed the frequency and amplitude parameters of the gastric slow wave from MGG. We identified normal gastric slow wave activity with a frequency of 2.6 +/- 0.5 cycles per minute (cpm) preprandial and 2.8 +/- 0.3 cpm postprandial. In addition to frequency and amplitude, the use of surface current density mapping applied to the multichannel MGG allowed us to visualize the propagating slow wave and compute its propagation velocity (6.6 +/- 1.0 mm s(-1) preprandial and 7.4 +/- 0.4 mm s(-1) postprandial). Whereas MGG and EGG signals exhibited strong correlation, there was very little correlation between the MGG and manometry. The MGG not only records frequency dynamics of the gastric slow wave, but also characterizes gastric propagation. The MGG primarily reflects the underlying gastric electrical activity, but not its mechanical activity.

Diabetic gastroparesis alters the biomagnetic signature of the gastric slow wave.

BACKGROUND: Gastroparesis is characterized by delayed gastric emptying without mechanical obstruction, but remains difficult to diagnose and distinguish from other gastrointestinal (GI) disorders. Gastroparesis affects the gastric slow wave, but non-invasive assessment has been limited to the electrogastrogram (EGG), which reliably characterizes temporal dynamics but does not provide spatial information. METHODS: We measured gastric slow wave parameters from the EGG and magnetogastrogram (MGG) in patients with gastroparesis and in healthy controls. In addition to dominant frequency (DF) and percentage power distribution (PPD), we measured the propagation velocity from MGG spatiotemporal patterns and the percentage of slow wave coupling (%SWC) from EGG. KEY RESULTS: No significant difference in DF was found between patients and controls. Gastroparesis patients had lower percentages of normogastric frequencies (60 ± 6% vs 78 ± 4%, p < 0.05), and higher brady (9 ± 2% vs 2 ± 1%, p < 0.05) and tachygastric (31 ± 2% vs 19 ± 1%, p < 0.05) frequency content postprandial, indicative of uncoupling. Propagation patterns were substantially different in patients and longitudinal propagation velocity was retrograde at 4.3 ± 2.9 mm/s vs anterograde at 7.4 ± 1.0 mm/s for controls (p < 0.01). No difference was found in %SWC from EGG. CONCLUSIONS & INFERENCES: Gastric slow wave parameters obtained from MGG recordings distinguish gastroparesis patients from controls. Assessment of slow wave propagation may prove critical to characterization of underlying disease processes. Future studies should determine pathologic indicators from MGG associated with other functional gastric disorders, and whether multichannel EGG with appropriate signal processing also reveals pathology.

Vector projection of biomagnetic fields.

Biomagnetic measurements are increasingly popular as functional imaging techniques for the non-invasive assessment of electrically active tissue. Although most currently available magnetometers utilise only one component of the vector magnetic field, some studies have suggested the possibility of obtaining additional information from recordings of the full magnetic field vector. Three projection techniques were applied to different biomagnetic signals for analysis of the three orthogonal components of the vector magnetic field. Vector magnetic fields obtained from fetal cardiac activity were projected into evenly spaced directions around a unit sphere. The vector magnetic field recorded from multiple intestinal current sources with independent temporal frequencies was then projected. Finally, an external reference signal from an invasive electrode was used to project the recorded vector magnetic fields due to gastric electrical activity. In each case, it was found that the information obtained by examination of the projected magnetic field vectors gave superior clinical insight to that obtained by analysis of any single magnetic field component.

Biomagnetic detection of gastric electrical activity in normal and vagotomized rabbits.

We recorded the vector magnetogastrogram (MGG) due to gastric electrical activity (GEA) in normal rabbits using a Superconducting QUantum Interference Device (SQUID) magnetometer and measured the degree of correlation of the MGG with 24 channels of serosal electrodes. The vector magnetometer allows us to non-invasively record three orthogonal magnetic field components and project the recorded magnetic field vector into arbitrary directions. We optimized the magnetic field vector direction to obtain the highest possible correlation with each serosal electrode recording. We performed a vagotomy and examined spatial and temporal changes in the serosal potential and in the transabdominal magnetic field. We obtained spatial information by mapping the recorded signals to the electrode positions in the gastric musculature. Temporal evidence of uncoupling was observed in spectral analyses of both serosal electrode and SQUID magnetometer recordings. We conclude that non-invasive recordings of the vector magnetogastrogram reflect underlying serosal potentials as well as pathophysiological changes following vagotomy.

The human vector magnetogastrogram and magnetoenterogram.

Electrical activity in the gastrointestinal system produces magnetic fields that may be measured with superconducting quantum interference device magnetometers. Although typical magnetometers have detection coils that measure a single component of the magnetic field, gastric and intestinal magnetic fields are vector quantities. We recorded gastric and intestinal magnetic fields from nine abdominal sections in nine normal human volunteers using a vector magnetometer that measures all three Cartesian components of the magnetic field vector. A vector projection technique was utilized to separate the magnetic field vectors corresponding to gastric and intestinal activity. The gastric magnetic field vector was oriented in a cephalad direction, consistent with previously observed data, and displayed oscillatory characteristics of gastric electrical activity (f = 3.03 +/- 0.18 cycles/min). Although the small bowel magnetic field vector showed no consistent orientation, the characteristic frequency gradient of the small bowel electrical activity was observed. Gastric and intestinal magnetic field vectors were oriented in different directions and were thus distinguished by the vector projection technique. The observed difference in direction of gastric and intestinal magnetic field vectors indicates that vector recordings dramatically increase the ability to separate physiological signal components from nonphysiological components and to distinguish between different physiological components.

An anatomical model of the gastric system for producing bioelectric and biomagnetic fields.

Between 60 and 70 million people in the United States are affected by gastrointestinal disorders. Many of these conditions are difficult to assess without surgical intervention and accurate noninvasive techniques to aid in clinical assessment are needed. Through the use of a superconducting quantum interference device (SQUID) gradiometer, the weak magnetic field generated as a result of muscular activity in the digestive system can be measured. However, the interpretation of these magnetic recordings remains a significant challenge. We have created an anatomically realistic biophysically based mathematical model of the human digestive system and using this model normal gastric electrical control activity (ECA) has been simulated. The external magnetic fields associated with this gastric ECA have also been computed and are shown to be in qualitative agreement with recordings taken from normal individuals. The model framework thus provides a rational basis from which to begin interpreting magnetic recordings from normal and diseased individuals.

Volume conductor effects on the spatial resolution of magnetic fields and electric potentials from gastrointestinal electrical activity.

An analysis of the relative capabilities of methods for magnetic and electric detection of gastrointestinal electrical activity is presented. The model employed is the first volume conductor model for magnetic fields from GEA to appear in the literature. A mathematical model is introduced for the electric potential and magnetic field from intestinal electrical activity in terms of the spatial filters that relate the bioelectric sources with the external magnetic fields and potentials. The forward spatial filters are low-pass functions of spatial frequency, so more superficial external fields and potentials contain less spatial information than fields and potentials near the source. Inverse spatial filters, which are reciprocals of the forward filters, are high-pass functions and must be regularised by windowing. Because of the conductivity discontinuities introduced by low-conductivity fat layers in the abdomen, the electric potentials recorded outside these layers required more regularisation than the magnetic fields, and thus, the spatial resolution of the magnetic fields from intestinal electrical activity is higher than the spatial resolution of the external potentials. In this study, two smooth muscle sources separated by 5cm were adequately resolved magnetically, but not resolved electrically. Thus, sources are more accurately localized and imaged using magnetic measurements than using measurements of electric potential.

Changes in intestinal electrical activity during ischaemia correlate to pathology.

The gastrointestinal tract possesses an omnipresent electrical slow wave called the basic electrical rhythm (BER). It has been shown that the frequency of the BER falls during intestinal ischaemia. The correlation between changes in the BER and pathology that occur during acute ischaemia are not completely understood. To study this, the electrical activity of the ileum in 14 adult male rabbits was recorded during ischaemia. At baseline, 60, 120 and 210 minutes of ischaemia, segments of bowel were resected for histopathologic evaluation. The BER frequency was determined using the Fast Fourier Transformation (FFT) spectral analysis. The BER amplitude and FFT spectral power were also determined. The results showed significant decrease (p<0.05, Student's T-test) in the BER frequency, amplitude, and spectral power at all time points. Between 60 and 120 minutes, while there was a decrease in BER activity the pathologic grade remained the same (focal loss of surface epithelium). By 210 minutes of ischaemia when the BER could not be recorded, there was diffuse mucosal infarction. The results indicate that changes in the electrical activity of the bowel during acute mesenteric ischaemia occurred prior to the pathologic changes. The presence of electrical activity indicates that there was viable bowel. Thus it should be possible to use recordings of electrical activity to evaluate bowel viability during acute ischaemia.

Histopathologic changes during mesenteric ischaemia and reperfusion.

The basic electrical rhythm (BER) of the intestine is known to decrease during mesenteric ischaemia. Some studies have reported the relationship between the BER and the pathologic changes that occur in the bowel during vascular injury. However, these changes have not been completely elucidated. This study describes the histopathologic pattern when the rabbit small intestine was subjected to ischaemia of varying time lengths (30-150 minutes) and subsequent reperfusion for six hours. Intestinal biopsies were taken at baseline, at the end of ischaemia, and at hourly intervals during reperfusion. Microscopic examination of the biopsies revealed evidence of progressive infarction of the mucosa during ischaemia. There was an acute worsening of the pathology during reperfusion, the severity being greater when reperfusion was preceded by longer periods of ischaemia. These changes were statistically significant. The observed pattern in this study shows clearly that reperfusion injury is reflected in the histopathologic response and that this is worse in severity than the response to ischaemia. Studies of longer duration should further clarify the picture during recovery in ischaemia/reperfusion injuries of the bowel.

Effects of body mass index on gastric slow wave: a magnetogastrographic study.

We measured gastric slow wave activity simultaneously with magnetogastrogram (MGG), mucosal electromyogram (EMG) and electrogastrogram (EGG) in human subjects with varying body mass index (BMI) before and after a meal. In order to investigate the effect of BMI on gastric slow wave parameters, each subject's BMI was calculated and divided into two groups: subjects with BMI ≤ 27 and BMI > 27. Signals were processed with Fourier spectral analysis and second-order blind identification (SOBI) techniques. Our results showed that increased BMI does not affect signal characteristics such as frequency and amplitude of EMG and MGG. Comparison of the postprandial EGG power, on the other hand, showed a statistically significant reduction in subjects with BMI > 27 compared with BMI ≤ 27. In addition to the frequency and amplitude, the use of SOBI-computed propagation maps from MGG data allowed us to visualize the propagating slow wave and compute the propagation velocity in both BMI groups. No significant change in velocity with increasing BMI or meal was observed in our study. In conclusion, multichannel MGG provides an assessment of frequency, amplitude and propagation velocity of the slow wave in subjects with differing BMI categories and was observed to be independent of BMI.

Noninvasive biomagnetic detection of isolated ischemic bowel segments.

The slow wave activity was measured in the magnetoenterogram (MENG) of normal porcine subjects (N = 5) with segmental intestinal ischemia. The correlation changes in enteric slow wave activity were determined in MENG and serosal electromyograms (EMG). MENG recordings show significant changes in the frequency and power distribution of enteric slow-wave signals during segmental ischemia, and these changes agree with changes observed in the serosal EMG. There was a high degree of correlation between the frequency of the electrical activity recorded in MENG and in serosal EMG (r = 0.97). The percentage of power distributed in brady- and normoenteric frequency ranges exhibited significant segmental ischemic changes. Our results suggest that noninvasive MENG detects ischemic changes in isolated small bowel segments.

Influence of body parameters on gastric bioelectric and biomagnetic fields in a realistic volume conductor.

Electrogastrograms (EGG) and magnetogastrograms (MGG) provide two complementary methods for non-invasively recording electric or magnetic fields resulting from gastric electrical slow wave activity. It is known that EGG signals are relatively weak and difficult to reliably record while magnetic fields are, in theory, less attenuated by the low-conductivity fat layers present in the body. In this paper, we quantified the effects of fat thickness and conductivity values on resultant magnetic and electric fields using anatomically realistic torso models and trains of dipole sources reflecting recent experimental results. The results showed that when the fat conductivity was increased, there was minimal change in both potential and magnetic fields. However, when the fat conductivity was reduced, the magnetic fields were largely unchanged, but electric potentials had a significant change in patterns and amplitudes. When the thickness of the fat layer was increased by 30 mm, the amplitude of the magnetic fields decreased 10% more than potentials but magnetic field patterns were changed about four times less than potentials. The ability to localize the underlying sources from the magnetic fields using a surface current density measure was altered by less than 2 mm when the fat layer was increased by 30 mm. In summary, results confirm that MGG provides a favorable method over EGG when there are uncertain levels of fat thickness or conductivity.

Biomagnetic and bioelectric detection of gastric slow wave activity in normal human subjects--a correlation study.

We measured gastric slow wave activity simultaneously with a Superconducting Quantum Interference Device (SQUID) magnetometer, mucosal electrodes and cutaneous electrodes in 18 normal human subjects (11 women and 7 men). We processed signals with Fourier spectral analysis and SOBI blind-source separation techniques. We observed a high waveform correlation between the mucosal electromyogram (EMG) and multichannel SQUID magnetogastrogram (MGG). There was a lower waveform correlation between the mucosal EMG and cutaneous electrogastrogram (EGG), but the correlation improved with the application of SOBI. There was also a high correlation between the frequency of the electrical activity recorded in the MGG and in mucosal electrodes (r = 0.97). We concluded that SQUID magnetometers noninvasively record gastric slow wave activity that is highly correlated with the activity recorded by invasive mucosal electrodes.

Characterization of gastric electrical activity using magnetic field measurements: a simulation study.

Gastric disorders are often associated with abnormal propagation of gastric electrical activity (GEA). The identification of clinically relevant parameters of GEA using noninvasive measures would therefore be highly beneficial for clinical diagnosis. While magnetogastrograms (MGG) are known to provide a noninvasive representation of GEA, standard methods for their analysis are limited. It has previously been shown in simplistic conditions that the surface current density (SCD) calculated from multichannel MGG measurements provides an estimate of the gastric source location and propagation velocity. We examine the accuracy of this technique using more realistic source models and an anatomically realistic volume conductor model. The results showed that the SCD method was able to resolve the GEA parameters more reliably when the dipole source was located within 100 mm of the sensor. Therefore, the theoretical accuracy of SCD method would be relatively diminished for patients with a larger body habitus, and particularly in those patients with significant truncal obesity. However, many patients with gastric motility disorders are relatively thin due to food intolerance, meaning that the majority of the population of gastric motility patients could benefit from the methods developed here. Large errors resulted when the source was located deep within the body due to the distorting effects of the secondary sources on the magnetic fields. Larger errors also resulted when the dipole was oriented normal to the sensor plane. This was believed to be due to the relatively small contribution of the dipole source when compared to the field produced by the volume conductor. The use of three orthogonal magnetic field components rather than just one component to calculate the SCD yielded marginally more accurate results when using a realistic dipole source. However, this slight increase in accuracy may not warrant the use of more complex vector channels in future superconducting quantum interference device designs. When multiple slow waves were present in the stomach, the SCD map contained only one maximum point corresponding to the more dominant source located in the distal stomach. Parameters corresponding to the slow wave in the proximal stomach were obtained once the dominant slow terminated at the antrum. Additional validation studies are warranted to address the utility of the SCD method to resolve parameters related to gastric slow waves in a clinical setting.

Biomagnetic signatures of uncoupled gastric musculature.

Gastric slow waves propagate in the electrical syncytium of the healthy stomach, being generated at a rate of approximately three times per minute in a pacemaker region along the greater curvature of the antrum and propagating distally towards the pylorus. Disease states are known to alter the normal gastric slow wave. Recent studies have suggested the use of biomagnetic techniques for assessing parameters of the gastric slow wave that have potential diagnostic significance. We present a study in which the gastric syncytium was uncoupled by mechanical division as we recorded serosal electric potentials along with multichannel biomagnetic signals and cutaneous potentials. By computing the surface current density (SCD) from multichannel biomagnetic recordings, we were able to quantify gastric slow wave propagation as well as the frequency and amplitude of the slow wave and to show that these correlate well with similar parameters from serosal electrodes. We found the dominant slow wave frequency to be an unreliable indicator of gastric uncoupling as uncoupling results in the appearance of multiple slow wave sources at various frequencies in external recordings. The percentage of power distributed in specific frequency ranges exhibited significant postdivision changes. Propagation velocity determined from SCD maps was a weak indicator of uncoupling in this work; we believe that the relatively low spatial resolution of our 19-channel biomagnetometer confounds the characterization of spatial variations in slow wave propagation velocities. Nonetheless, the biomagnetic technique represents a non-invasive method for accurate determination of clinically significant parameters of the gastric slow wave.

Spatial filter approach for evaluation of the surface Laplacian of the electroencephalogram and magnetoencephalogram.

The surface Laplacian is a technique that has been utilized to improve the spatial resolution of the electroencephalogram (EEG) and the magnetoencephalogram (MEG). We investigate the amount of improvement to the spatial resolution afforded by the surface Laplacian by examining the spatial filters that describe the relationship between cortical current sources and the surface Laplacian. The surface Laplacian spatial filters extend into higher spatial frequencies than do raw signal spatial filters, particularly for EEG Laplacian spatial filters, indicating that substantial improvement in spatial resolution is possible. However, the response of the surface Laplacian operation to the nature and amount of noise in the raw EEG and MEG signals is of paramount importance. Spatially correlated noise, coupled with uncorrelated noise, requires additional regularization of inverse spatial filters resulting in a decrease in spatial resolution. Substantial improvements in spatial resolution may be obtained using the surface Laplacian techniques as long as correlated noise levels are small and raw signals have relatively high signal-to-noise ratios.

Spatial filter approach for comparison of the forward and inverse problems of electroencephalography and magnetoencephalography.

We present an analysis of the relative information content of cortical current source reconstructions from electroencephalogram (EEG) and magnetoencephalogram (MEG) forward calculations by examining the spatial filters that relate the internal sources with the externally measured electric potentials and magnetic fields. The forward spatial filters are seen to be low-pass functions of spatial frequency and spatial resolution degrades in external measurements. Inverse spatial filters may be used to reconstruct cortical sources from external data, but since they are high-pass functions of spatial frequency, they must be regularized to avoid instabilities caused by noise at higher spatial frequencies. The regularization process limits the spatial resolution of source reconstructions. EEG forward spatial filters fall off at lower spatial frequencies than MEG filters; hence, there is less information available in higher spatial frequencies resulting in lower spatial resolution in inverse reconstructions. The tangential component of the magnetic field provides even higher spatial resolution than can be obtained using the radial component. An accompanying article examines the surface Laplacian for both the EEG and the MEG.

Correlation and comparison of magnetic and electric detection of small intestinal electrical activity.

The small intestinal basic electrical rhythm (BER) was detected simultaneously with serosal electrodes and a transabdominal superconducting quantum interference device (SQUID) magnetometer in anesthetized rabbits. We induced mesenteric ischemia to correlate serosal electrode recording of changes in BER with the SQUID magnetometer. The BER frequency was obtained by spectral analysis of the data using Fourier and autoregressive techniques. There was a high degree of correlation (r = 0.96) between the BER frequency determined using the serosal electrodes and the BER frequency ascertained from SQUID data. Additionally, the effects of an electrical insulator on the external electric and magnetic fields were studied in the rabbit model. The presence of an insulator profoundly attenuates external electric potentials recorded by cutaneous electrodes but does not significantly affect external magnetic fields or serosal potentials. We conclude that SQUID magnetometers could noninvasively record small intestinal BER that was highly correlated with the activity recorded by invasive serosal electrodes. The advantages of magnetic field measurements have encouraged us to investigate clinical applications.

Noninvasive diagnosis of mesenteric ischemia using a SQUID magnetometer.

OBJECTIVE: The authors assessed the ability of a Superconducting Quantum Interference Device (SQUID) magnetometer to noninvasively detect mesenteric ischemia in a rabbit model. SUMMARY BACKGROUND DATA: Superconducting Quantum Interference Device magnetometers have been used to detect magnetic fields created by the basic electrical rhythm (BER) and to detect changes in BER of exteriorized bowel of anesthetized rabbits during mesenteric ischemia. METHODS: The BER of rabbit ileum was noninvasively measured transabdominally using a SQUID magnetometer and compared with the electrical activity recorded with surgically implanted serosal electrodes before, during, and after snare occlusion of the superior mesenteric artery. RESULTS: Transabdominal SQUID recording of BER frequency was highly correlated to the measurements obtained with electrodes (R = 0.91). Basic electrical rhythm frequency decreased from 16.4 +/- 0.8 to 8.3 +/- 0.3 cpm (p < 0.001) after 25 minutes of ischemia. Reperfusion of ischemic bowel resulted in recovery of BER frequency to 14.3 +/- 0.4 cpm 10 minutes after blood flow was restored. CONCLUSIONS: A SQUID magnetometer is capable of noninvasively detecting mesenteric ischemia reliably and at an early stage by detecting a significant drop in BER frequency. These positive findings have encouraged the authors to continue development of clinically useful, noninvasive, detection of intestinal magnetic fields using SQUID magnetometers.