Magnetic resonance imaging for gastric motility and function
Magnetic resonance imaging (MRI) is a valuable tool for visualization of the anatomy and the function of the digestive system in health and disease . Use of MRI in assessment of gastric physiology was proposed and validated against gastric scintigraphy and intraluminal pressure measurement (barostat, manometry) in the 1990s and 2000s . Since then studies have demonstrated its utility in the measurement of gastric contractility (phasic contraction waves), tonic relaxation during meal ingestion (often referred to as “accommodation”) and tonic contraction after the meal . Sequential application of specific MRI acquisition parameters can also assess the distribution, volume and emptying of gastric contents (meal and secretion) . The near simultaneous measurement of multiple aspects of gastric function during and after the meal provides unique insights into the mechanisms that control gastric motility and function . Additionally, concurrent recording of symptoms during these studies reveal factors involved in generating filling sensation and satiety in health, and dyspeptic symptoms in functional dyspepsia, gastroparesis and related conditions .
Conventional techniques limited to measurements of a single aspect of gastric function (e.g. emptying) do not adequately address the complex GI response to feeding. Moreover these techniques are often invasive disturbing normal physiology (e.g. barostat), involve exposure to radioactive isotopes (e.g. scintigraphy), user dependent (e.g. ultrasound), or provide only indirect assessment of gastric function (e.g. 13 C breath tests) . Several characteristics make MRI an ideal technique for the direct assessment of gastric structure and function. This form of imaging acquires large field-of-view, dynamic, high-resolution, three-dimensional (3D) image data with excellent soft-tissue contrast in less than a second; it does not expose subjects to ionizing radiation, it is non-invasive and the acquisition and analysis of the images can be independently verified . However, in practice, although MRI has advantages over other techniques used for this purpose, there are challenges involving processing of MRI data for fast, accurate and efficient characterization of images.
Gastric morphology and volume measurement: Image acquisition and analysis
The stomach has a complex three-dimensional (3D) anatomy that must be reconstructed from two-dimensional (2D) cross-sectional MR images acquired in standard anatomical planes (i.e. sagittal, coronal, transverse) . The first step in achieving this goal is to filter the images digitally to achieve better contrast for the region of interest (ROI). To facilitate this step, paramagnetic contrast agent (e.g. Gadolinium DOTA) can be added to test meals. Then the ROI is segregated from the other adjacent anatomical structures captured in the images, a step known as image segmentation. The conventional way of doing this is to manually identify sufficient number of points on the edge of the ROI and join them with straight lines to generate the contours of the ROIs, i.e., segmentation of the images. Once all the contours belonging to the ROI in all the 2D image slices are identified, then these can be covered with a surface using 3D reconstruction computer algorithms . Manual analysis of this data is tedious and time consuming, as forty or more image slices are required to capture the ROI in its entirety at each time point during gastric filling and emptying (typically every 5–15 minutes during a 2 hour gastric emptying study). Moreover, this method of image analysis requires expert personnel for accurate image segmentation. These limitations have restricted the adoption of this technique to a few specialist centers.
The simplest method used to extract objective measurements of 3D volume from MR images is based on thresholding, i.e., segregation of regions within images depending on whether they fall below a particular image intensity threshold and are adjacent to neighboring pixels of similar intensity, to form contiguous areas . In the analysis of MR images from the stomach, the search domain is not restricted to neighboring pixels in one particular image slice through the stomach. Rather it can be expanded to include neighboring pixels in adjacent slices to generate the volume of “objects” within a ROI that share the same image intensity. This approach is useful for (relatively) rapid estimate of gastric content volume with gastric air and gastric meal volumes assessed separately . Image quality and the contrast play a crucial role in controlling the efficiency of this algorithm because the semi-automatic measurements are confounded by the presence of adjacent objects with similar image intensity. This can be an issue with the stomach, especially if a normal, mixed solid and liquid test meal with heterogeneous content is ingested. Further the resolution of the 3D images acquired by this technique is not high. Nevertheless, thresholding is very useful for measurement of complex structures with relatively homogeneous content like the small intestine .
Recently, a semi-automatic method has been developed, to generate high-resolution 3D reconstructed geometry in a rapid and efficient manner . The user generates virtual MR images (usually 3–4) along arbitrary planes by manually selecting a few points on the ROI (e.g. stomach wall) in a number of 2D images within the stack such that the planes pass through the stomach in multiple images ( Fig. 14.1A ). The complexity of the ROI determines the number of virtual slices to be segmented. The segmentation of the virtual images generates contours, which intersect the original images and these “seed points” at the edge of the ROI in the original image give cues for the computer to further segment the original images ( Fig. 14.1B ). The order of joining the points is determined using an algorithm, referred to as “magnetic linking” based on the local image intensity gradient in the image and joined automatically using edge detection algorithms (e.g. livewire) to generate high-resolution 3D images the original 2D MR slices . Further this technique can be adapted to assess changes to 3D geometry over time by using a representative image from within a series of images as reference to process adjacent image stacks automatically. This generates four-dimensional (4D) reconstructions that document dynamic gastric function in terms of volume change and alterations in gastric morphology during gastric filling and emptying . The advantage of this method over the manual approach is that it substantially reduces user input and the time required for image processing. The number of slices to be segmented is reduced drastically (approximately 90% less) and requires an estimated 100 mouse clicks, as opposed to that 10,000 mouse clicks in the conventional procedure . The 3D reconstruction of gastric morphology is expedited using this semi-automated method; however, this method is dependent on access to high-end computing technology and still requires more time to perform than the above mentioned thresholding technique .
Insight into the functional anatomy of the stomach can be obtained by dividing the 3D geometry of the organ in the computer environment into different segments and finding the variation in the volume of these segments over time. Usually the stomach is divided into proximal and distal region, however, more division may provide more information about how the stomach accommodates food and delivers nutrients to the small bowel ( Fig. 14.3 ) . Detailed results from non-invasive imaging confirm the functional division of the stomach. After initial filling of the distal and mid stomach (antrum and corpus), the meal is accommodated in the proximal stomach (fundus). Similarly, once the meal is completed, volume in the distal and mid-stomach remains relatively stable until the proximal stomach is almost empty .
Gastric motility (phasic contractions)
After meal ingestion peristaltic, often non-occlusive contractions migrate distally from the corpus to the antrum. When the contraction wave approaches the pylorus, the sphincter narrows, forcing the gastric contents back into the body of the stomach. Together with chemical and enzymatic digestion, this mechanical process (trituration) mixes and grinds solid matter into a somewhat homogeneous mixture (chyme) ready for passage through the pylorus into the small bowel.
Analysis of the MRI images can quantify frequency, velocity (or periodicity) as well as occlusion amplitude and width of gastric contraction waves at either predefined positions or over the length of the distal stomach . Image planes positioned obliquely along the long axis of the stomach are used to assess gastric motility using MRI ( Fig. 14.4 ). On the modern scanners, high-resolution, ultra-fast imaging of a single slice with a frame rate of 3–4 per second can be applied for image acquisition. This timescale still allows gastric contractions to be followed closely as they progress distally towards the pylorus. Alternatively, a bigger gastric area can be covered by acquiring a stack of three parallel image slices at a rate of 1 per second. Recently, technological advances in the MRI field, mainly driven by cardiac applications, have provided new tools for dynamic (or “cine”) body imaging. Such approaches can be extended to GI applications. For instance, MRI acceleration techniques can reduce acquisition times, allowing for full 3D gastric coverage with excellent spatial resolution, whilst maintaining adequate temporal resolution to capture peristaltic contractions. These technological advances will facilitate clinical imaging because rapid acquisition over a large region of interest compensates for changes in gastric position over time due to gastric emptying, respiratory motion and patient movement. MRI also allows the detection of gastric flow events and has been used to demonstrate association of antral motility with substantial forward and backward flow across the pylorus rather than simple, unidirectional peristaltic bolus transport .
The limitation of MRI (as with other imaging methods) is that it does not provide direct measurements of pressure events in the stomach, pylorus and small bowel. Although technically demanding, MRI has been combined with intra-luminal barostat and various forms of gastro-duodenal manometry to provide a comprehensive assessment of gastric function . Results suggest that gastric emptying of nutrient liquids occurs primarily due to tonic pressure generated by the stomach wall during long episodes of relative antral quiescence, controlled by pyloric opening and possibly distal duodenal activity . These results indicate that the gastroduodenal pressure gradient rather than a “peristaltic pump” is the main mechanism driving gastric emptying after the meal.
In the past, gastric secretion could only be investigated by invasive intubation techniques. These are unpleasant, generally assess only the proximal stomach and may themselves influence the production of secretions. Two MRI techniques have been developed and validated to assess the volume of gastric secretion. Gastric secretion can be measured via the reduction of meal viscosity due to dilution by mapping the T2 relaxation time of hydroxyl protons on polysaccharide molecules . Alternatively, the recorded meal signal intensity of a test meal labeled with a paramagnetic marker can be normalized with reference to a simultaneously recorded ex-vivo reference. can be calculated using MRI . By repeatedly mapping the T1 relaxation times of the gastric content at normal image resolution, not only the volume of secretion, but also the local dilution process caused by secretion and mixing can be monitored and quantified .
Application of the dilution marker technique demonstrates considerable inter-individual variation in gastric secretion and inhomogeneous distribution of secretion within the stomach . MRI documents how gastric secretions collect in the stomach after a meal ( Fig. 14.5 ). It shows how the mucosa secretes a distinct layer of fluid “around” the meal at the periphery and, in particular, how secretion collects in the proximal stomach at the level of the oesophago-gastric junction (the co-called “acid pocket”) . MRI has also shown how anti-reflux medications, such as alginates and proton-pump inhibitors, either displace the acid pocket or reduce the volume of acid secretion .
Gastric emptying is a complex process and a universally accepted description of the physiology and control of this process has not been established. Variation in gastric tone and contractile activity together with pyloric and duodenal resistance all impact on the rate at which ingested material is delivered to the small bowel. The advantage of MRI is that, unlike other techniques, sequential application of specific acquisition parameters can monitor multiple aspects of gastric function under physiological conditions. This facility has provided insights into how the volume and energy density of the meal modulate gastric emptying . MRI has also shown how this process is affected by the physical and chemical properties of the meal (e.g. solid vs. liquid, macronutrient composition), the intragastric distribution of gastric contents and body position during emptying . The technique is also sensitive to pharmacological and endoscopic interventions that modulate the rate of gastric emptying .
As described above, the total gastric volume and gastric content volume are identified by distinct positive contrast and outlined on the MRI images. With positive paramagnetic contrast markers gastric volume can be corrected for gastric secretions. The time plot of corrected gastric volumes provides a direct assessment of the gastric emptying half time (t50), residual volume at defined time points and other standard measurements. MRI has been validated against scintigraphy for liquid and mixed solid/liquid meals . The results correlate closely for patients over a wide range of gastric emptying times in health and disease, including diabetic gastroparesis . However, MRI reveals the dynamic pattern of volume change during and after meal ingestion ( Fig. 14.6 ). It has been shown that gastric emptying commences during intake of a liquid nutrient meal as evidenced by the presence of chyme labeled with paramagnetic contrast in the small bowel in the first image acquired after meal ingestion. This “early-phase” emptying is followed by a “late-phase” linear–exponential reduction in meal volume. Analysis of the imaging data indicate that “early-phase” GE is related only to the volume load ingested, whereas “late-phase” emptying is modulated by volume and calorie load . These findings strongly suggest that (i) it is not appropriate to normalize volume after meal ingestion because a substantial and variable amount of emptying (5%–25% of meal volume) has already occurred at this timepoint and (ii) it is not adequate to describe gastric emptying using a single measurement (e.g. T50, retention time at 2 hours).