WO2014165055A1

WO2014165055A1 - Magnetic Resonance Triggering System for Swallowing and Speech Dynamic Imaging

Info

Publication number: WO2014165055A1
Application number: PCT/US2014/024259
Authority: WO
Inventors: Emi Zuiki MURANO; Jerry L. Prince; Li Pan
Original assignee: The Johns Hopkins University; Siemens Corporation
Priority date: 2013-03-12
Filing date: 2014-03-12
Publication date: 2014-10-09

Abstract

An embodiment in accordance with the present invention provides a novel technique of MRI acquisition and analysis to provide new data on the swallowing-related structural and functional consequences in post-treatment sequelae in OPSCC. The method of MRI acquisition includes configuring an MRI machine to take a tagged MRI image (tMRI). The method also includes indicating to the subject that she should prepare to swallow by taking a sip of a liquid, as well as indicating for the subject to swallow the liquid. The MRI machine is triggered to acquire images and synchronized such that the acquisition of the images occurs during the swallowing of the liquid. The images can be further processed in order to learn additional information regarding the subject's mechanics of swallowing.

Description

Magnetic Resonance Triggering System for Swallowing and Speech Dynamic Imaging

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 61/777,235 filed on March 12, 2013, which is incorporated by reference, herein, in its entirety.

FIELD OF THE INVENTION [0002] The present invention relates generally to imaging. More particularly the present invention relates to a method for the imaging of swallowing using tagged MRI. BACKGROUND OF THE INVENTION

[0003] Assessment of tissue motion is useful in the early diagnosis of certain diseases and surgical planning. This is especially true for the heart, tongue, and other organs with movement based primarily on that of the underlying muscle. While such visualization would be useful in diagnostic and surgical settings, medical imaging would be needed to give the necessary views. Medical imaging of tissue motion is contingent on synchronizing the capture of the image with the subjects voluntary or involuntary movements. Such synchronization is difficult and can include user error based on an event such as an improperly signaled subject or an improperly timed image capture. Such synchronization would also require communication between and therefore a connection between several complicated pieces of equipment, which is not available.

[0004] Head and neck squamous cell carcinoma (HNSCC) account for 5% of all malignancies worldwide and it is the sixth most common cancer in the United States. Although the survival rate in 5 years is as high as 66%, comorbidity is huge. The head and neck deformation, swallowing and speech articulation dysfunction are the three main incapacitating reasons lowering quality of life (QOL) and as low as 48% of treated patients return to work. Over the last 20 years, an increase in the world-wide incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been observed A five-fold increase of OPSCC among young men and six-fold increase among young women ages 20 to 44 has been reported. It also has been considered that a new clinical and molecular disease entity of OPSCC is associated with an active sexually transmitted human papillomavirus infection (HPV). The OPSCC with HPV(+) differ in prognosis, recurrence, and ethnical incidence from those OPSCC HPV(-) with a previous history of smoking and alcohol drinking. The HPV(+) responds better to cancer treatment than HPV(-) (in 3 -year follow up), but has a higher recurrence rate (20% in 10-year follow up), indicating the cancer becomes indolent and needs a longer follow-up strategy.

[0005] While the US population-level incidence of OPSCC HPV(-) declined by 50% from 1984 to 2004, an alarming increase of 225% was observed for OPSCC HPV(+) for the same period. Furthermore, the prevalence of oral HPV infection in the US is estimated to be 6.9%, more prevalent in white males, and with two age peaks of 30 to 34 years and 60 to 64 years old. These numbers indicate that preventive methods such as public awareness of this disease entity and HPV vaccination, as well as, better options of treatment and improvement of QOL for those OPSCC and other HNSCC patients are very important.

[0006] Among the new treatments, intensification treatment, such as concomitant radiation (RT) and chemotherapy, fractionated RT has shown better control of the disease. However, an increase in dysphagia resulting from such treatment has been observed. In order to improve the QOL, intensity-modulated RT (IMRT) has been proposed and applied. This method allows for the sparing of structures (glands, muscles) that are related to dysfunction commonly observed post-chemoradiation. Avoiding salivary glands and pharyngeal constrictors muscles has shown decrease in the xerostomia and acute and later onset dysphagia respectively. [0007] Detailed observations of motions of the entire tongue, soft palate, pharynx, and larynx have been made extensively from video fluoroscopy (VF) with ingestion of distinct amounts and consistency of food. The VF is the gold standard for clinical use and is still used for research. Also, there have been studies of the movements of several pellets marker on the tongue surface and surface suction cups in the pharyngeal muscosa. Although these studies have been very useful for some quantitative purposes, there are some limitations in the method. It is a method that relies on the contrast medium where the bolus contrast and it contact with the mucosa provides the most prominent information; bone structures are clearly seen with overlap of several structures; axial view is not possible; use of ionizing wavelength that limits the amount of exposure of subject. The most challenging limitation of VF incurs on the variability of the VF interpretation. To overcome this MBS imp rating system has been implemented, but there is still a need of training, certification and reevaluation between group of raters so results can be comparable among raters and subjects/patients. However, VF is a qualitative method of determining dysfunction in swallowing. The information is observed but no quantitative analysis can be done.

[0008] It would therefore be advantageous to provide a new, more accurate, quantitative method for allowing for the identification of key structures and their position during the swallowing process in order to reduce dysphagia in patients being treated for HPV (+) and HPV (-) OPSCC.

SUMMARY OF THE INVENTION

[0009] The foregoing needs are met, to a great extent, by the present invention, wherein in one aspect method of imaging an event of swallowing of a subject includes configuring a magnetic resonance imaging (MRI) machine to take a tagged magnetic resonance image of the subject and indicating for the subject to swallow. The method further includes triggering the MRI machine to acquire images of the subject during a swallow made by the subject and synchronizing the indicating for the subject to swallow with the triggering of the MRI machine to acquire images of the subject.

[0010] In accordance with an aspect of the present invention, the method further includes indicating for the subject to prepare to swallow by taking a sip of a liquid. The liquid can take the form of a contrast liquid. The indicating to swallow can take the form of an auditory cue, such as a beep or a double beep. A single beep can be used to indicate that the subject should prepare to swallow, and a double beep can be used to indicate that the subject should swallow. The MRI machine is triggered to acquire images when the subject swallows. The subject is imaged during the swallow for 2 seconds. Additionally, the subject can engage in a 20 second swallowing cycle, repeatedly swallowing over the 20 second swallowing cycle.

[0011] In accordance with another aspect of the present invention, a system for imaging an event of swallowing of a subject includes a magnetic resonance imaging machine configured to take a tagged magnetic resonance image of the subject during an event of swallowing. The system also includes a device for indication configured to play an indication for the subject to swallow. Additionally, the system includes a trigger in communication with the magnetic resonance imaging machine configured to cause the magnetic resonance imaging machine to capture the tagged magnetic resonance image of the subject. The indication for the subject to swallow and the trigger are synchronized to capture the tagged magnetic resonance image of the subject during the event of swallowing.

[0012] In accordance with yet another aspect of the present invention, the system includes a liquid for the subject to swallow. The liquid can take the form of a contrast liquid. In the system, the device for indication takes the form of an auditory cue. Further, the indication takes the form of a double beep. The indication can also include a pre-indication indicating that the subject should prepare to swallow. The pre-indication can take the form of a single beep. In accordance with the system, the magnetic resonance imaging machine images for a predetermined period of time during the event of swallowing. The predetermined period of time is approximately 2 seconds. The subject can also engage in a 20 second swallowing cycle, repeatedly swallowing, while the magnetic resonance imaging machine is

synchronously triggered for imaging, such that the predetermined time for imaging is approximately 20 seconds.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The accompanying drawings provide visual representations, which can be used to more fully describe the representative embodiments disclosed herein and can be used by those skilled in the art to better understand them and their inherent advantages. In these drawings, like reference numerals identify corresponding elements and:

[0014] FIG. 1 illustrates a schematic diagram of an exemplary setup to execute the method of the present invention.

[0015] FIG. 2 illustrates velocity fields in two consecutive time frames of t-MRI data from a normal subject 44-year-old female subject, according to the method of the present invention.

[0016] FIGS. 3-5 illustrate exemplary results obtained from the method described above, with respect to the present invention.

DETAILED DESCRIPTION

[0017] The presently disclosed subject matter now will be described more fully hereinafter with reference to the accompanying Drawings, in which some, but not all embodiments of the inventions are shown. Like numbers refer to like elements throughout. The presently disclosed subject matter may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements. Indeed, many modifications and other embodiments of the presently disclosed subject matter set forth herein will come to mind to one skilled in the art to which the presently disclosed subject matter pertains having the benefit of the teachings presented in the foregoing descriptions and the associated Drawings. Therefore, it is to be understood that the presently disclosed subject matter is not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims.

[0018] An embodiment in accordance with the present invention provides a novel technique of MRI acquisition and analysis to provide new data on the swallowing-related structural and functional consequences in post-treatment sequelae in OPSCC. The method of MRI acquisition includes configuring an MRI machine to take a tagged MRI image (tMRI). The method also includes indicating to the subject that she should prepare to swallow by taking a sip of a liquid, as well as indicating for the subject to swallow the liquid. The MRI machine is triggered to acquire images and synchronized such that the acquisition of the images occurs during the swallowing of the liquid. The images can be further processed in order to learn additional information regarding the subject's mechanics of swallowing.

[0019] The MRI data on tissue deformations and stresses within the tongue, suprahyoid, pharyngeal, soft palate muscles can also be used to investigate mechanisms underlying complex movements in healthy controls and the strategies that individual OPSCC patients develop to compensate for their post-treatment deficits. Also, the t-MRI method provides quantifiable and data-driven results that are not dependent on the person analyzing the data. The topological and functional identification of the structures related to normal and dysfunctional swallowing will enable radioncologist planning to spare those structures for a better functional outcome. Additionally, pre- and post-treatment intra-subject, comparison of treatments measuring functional outcomes studies will be available with the present method. [0020] FIG. 1 illustrates a schematic diagram of an exemplary setup to execute the method of the present invention. FIG. 1 illustrates a subject positioned on the bed of an MRI machine. The subject wears headphones or listens to speakers in the MRI machine or the imaging suite, in order to hear auditory cues for preparing to swallow and swallowing. A single auditory cue such as a beep is sounded to indicate that the subject should prepare to swallow. A quickly repeated auditory cue, such as a double beep is sounded to indicate that the subject should complete swallowing. When the subject is cued to prepare to swallow, the subject can take a sip of a liquid. The liquid can take the form of a contrast liquid, such as pineapple juice, gadolinium, energy drinks, milk of magnesia, orange juice, or blueberry juice. When the subject is cued to swallow, the subject swallows the liquid. A plastic straw and a glass or plastic cup can be used to deliver the liquid to the subject.

[0021] Further with respect to FIG. 1, the subject can be asked to repeat the swallowing protocol, described above, several times. The swallowing protocol is preferably repeated at least two to four times. However, longer swallowing sequences can be initiated as known to one of skill in the art. For instance, the subject can execute the swallowing protocol for two seconds each time and repeat the swallowing protocol over a 20 second time frame. The MRI machine is triggered to acquire images, when the subject swallows, and can be triggered repeatedly based on the number of times the subject will be indicated to swallow. In a case of repeated swallowing it is crucial that the MRI machine be synchronized to the indication to swallow.

EXAMPLE

[0022] An exemplary implementation of the present invention is described herein, in order to further illustrate the present invention. The exemplary implementation is included merely as an example and is not meant to be considered limiting. Any implementation of the present invention on any suitable subject known to or conceivable by one of skill in the art could also be used, and is considered within the scope of this application.

[0023] For the experiments, contrast swallowing was chosen over dry swallowing for three reasons: (1) subjects will swallow several times and should be able to repeat the swallowing rhythmically. Deliver of same amount of liquid will be helpful for this achievement. More than two dry swallows are not easily performed, and patients post-treatment might suffer from xerostomia; (2) visualization of the bolus will enable determining the oral, pharyngeal and passage of the bolus through the upper esophageal sphincter swallowing phases; and (3) the mucosa-bolus boundary may enable the countering of the 3D surface.

[0024] Previous studies on real-time MRI in swallowing have used gadolinium, energetic drinks and pineapple or blueberry juices containing high levels of magnesium and iron. To select the best contrast medium for the swallowing study, containers with 100 ml of water, pineapple juice, pineapple juice and orange, blueberry juice, and milk of magnesia were scanned using three MRI sequences, the commercial available t-MRI, Siemens real-time, and structural 3D MRI acquisition. The scale from brightest white to gray was pineapple juice, pineapple juice and orange, blueberry jelly, milk of magnesia and water. Commercially available pineapple juice was selected for the subsequent experiments. Other liquids or foods could also be used.

[0025] In order to obtain one slice of 18 time-frames/second (18Hz) of t-MRI CSPAMM images, subjects need to repeat five rhythmic swallows. Therefore, the subject's ability to repeat the swallowing precisely is critical to image quality. Variability across swallow repetitions causes blurring of images and crossing of tags when the images are combined for analysis in HARP. While the HARP software is used as an example herein, any analysis software known to or conceivable by one of skill in the art could also be used. Repeatability inside the MRI was possible due to a delivery of acoustic cues to synchronize swallowing repetitions with MRI acquisition. A synchronization technology improves the precision of the subject's repetitions with the use of an auditory cue. The audio system of the MRI console delivers short white-noise pulses to the subject through headphones, and triggers the MRI acquisition synchronously. Two subjects trained outside the scanner using a 2mm diameter plastic tube connected to a glass container with pineapple juice. They were positioned in the supine position and requested to sip the juice and swallow rhythmically according to the acoustic cue. Each swallow cycle has a 2 second duration. Real-time MR images were obtained for 20 seconds using the same method used in the training of both subjects. They both were able to complete 30 minutes of dynamic and static scans. The duration of cycles was measured to check accuracy was measured in the second subject using the temporal mode window similar to those used in high-speed-digital imaging of vocal folds open-closed quotient or M-mode in ultrasonography. The average period length of swallowing cycles from the measurement of nine cycles of opening of the pharynx, elevation of the larynx, entrance of contrast inside the mouth, soft-palate elevation, horizontal and vertical movement of hyoid bone from sagittal rt-MRI was 2050ms (+/-52ms).

[0026] A tagged-MRI CSPAMM sequence was implemented in the research Siemens 3- Tesla MRI system. Three sagittal slices of 10mm of thickness at 18Hz were acquired and analyzed using the HARP 3D software.

[0027] As illustrated in FIG. 2, velocity fields in two consecutive time frames of t-MRI data from a normal subject 44-year-old female subject are obtained. This pattern has never been seen in a previously examined normal subject. The vortex core seems to be a "critical point," which is defined as a stationary or zero-motion location, around which all neighboring points are moving. This counterclockwise rotation occurs at the end of the pharyngeal phase and it is followed by a clockwise rotation 165ms later. [0028] Patients develop individual compensation strategies to optimize their swallowing output, and those strategies depend on the dose radiation and the physiological importance of the affected muscle to the swallowing. To test this hypothesis, a study using h-MRI and t- MRI can be conducted to relate internal tissue deformation patterns to those found in normal subject. These variables can be determined by the radiation dosimetry values obtained from each OPSCC patient post treatment at the Department of radiological Oncology delivered in the IMRT. Dosimetric values of salivary glands, pharyngeal constrictors, tongue and submental muscles and larynx can be determined. The MRI protocols for t-MRI and realtime can be the same as those used in the data acquisition in the preliminary experiment. HARP can be used to analyze the data.

[0029] A 4D version of HARP is currently being developed to analyze multiple orthogonal MRI data sets and can be used as well to obtain the 4D t-MRI in swallowing. Normative data can be collected in 10 control subjects, so the kinesiology in swallowing can be compared to patients.

[0030] Additional improvements to the method can include (1) the development of a delivery system of same amount of contrast into the subjects mouth; (2) program a sequential slices acquisition plan in three orthogonal planes and feasible for both subjects and patients, so they can swallow comfortably but is a limited period of time. (3) find better parameters of acquisition of data for the laryngeal and upper esophageal area, which did not showed robust tagged results as seen in the tongue, suprahyoid and pharyngeal regions. The method may also include having the subject's hearing tested (with a standard audiometric screening test) before the MRI scan. This is necessary, because it is essential that they are able to follow the acoustic cues to perform rhythmic swallows. (4) Automation of the delivery of contrast. [0031] Additionally, the method can include a pre-treatment VF, and at least one VF six and twelve months after treatment. Some might have VF during or just after treatment due to clinical dysphagia evaluation.

[0032] An oral motor function evaluation can be administered prior to data collection. A train session mimicking the MRI room set up with the acoustic cue and swallowing can also be employed. Ability to swallow without choking and synchrony with the acoustic timing cue to be used with the MRI can be tested.

[0033] All MRI data can be collected in the sagittal, coronal and axial planes for each subject. Subjects will wear headphones for noise reduction and to be able to hear the experimenter and the acoustic cue. Real-time MR and t-MRI can be collected during swallowing of juice. For the 3D h-MRI, the operator can scan the vocal tract while the subject holds still in a quiet breathing task. Each h-MRI scan takes a maximum of three minutes.

[0034] HARP can be used to extract tissue point displacements, velocities, principal strains, and strain in the line-of-action of specific muscles from the tMRI. HARP extracts values for every tissue point in the tongue in 3D (2D + temporal) or in 4D (3D + temporal) dimension resulting in a very dense data set. The data can be visualized at any level of density (the 4D principal strain and 3D velocity figures throughout this proposal have been downsampled according to user specification). In addition, user-specified points can be tracked and Lagrangian strains calculated in the line of action of a muscle. Average values of displacement, velocity and strain can be calculated for user-defined regions.

[0035] There can be two independent segmentation in the MRI from this study and CT-

MRI acquired for clinical staging, radiation planning. (1) h-MRI 3D static data can be segmented and labeled using ITK-snap and MIPAV. This 3D image can be registered into the

4D real-time MR and 4D t-MRI. Average displacement and principal strains can be calculated for regions (muscle or muscle grouping) from t-MRI data for a specific motion or swallowing phase. Lagrangian strains, which measure strain between two endpoints in a specific muscle (consider the muscle from origin to insertion as in vector analysis), can be calculated to further support the inference of apparent muscle activity. Muscle activity is inferred, and cannot be calculated from compression data. Tagged-MRI strain data provide compression and expansion of tissue, which can be active or passive. In case of active, it may be in the same orientation of the vector line of the muscle. (2) the segmentation of the muscles and structures used in the planning console can allow the calculation of the dose of radiation applied to each patient. Determining asymmetry and which structure has changes in strain (lack of deformation such as rigidity) can be also compared to dosimetric results post- treatment.

[0036] The kinematic data from t-MRI from muscles and from larger regions such as group of muscles of upper pharynx, right and left from each subject can be measured on a case-by- case basis and the results can be summarized. On the basis of this summary, a subset of independent variables can be identified (tumor and patient characteristics) and dependent variables (from the radiation dosimetric study and chemoradiation regimen, neck surgery). Values of this subset of variables can be entered into a database and can then examine relations among them using such techniques as multiple regression, partial correlation and analysis of variance. The results of these analyses should provide much more useful insight into swallowing function than has been available to date.

[0037] FIGS. 3-5 illustrate exemplary results obtained from the method described above, with respect to the present invention. FIG. 3 illustrates a tagged-MRI and a high-resolution

MRI in order to show internal tissue deformation and velocity fields. FIG. 4 illustrates an image of a genihyoid muscle of a subject, as well as a graph of strain plotted as a function of time. The graph shows tissue expansion and tissue compression during the subject's swallow. FIG. 5 illustrates an image of a genioglossus muscle of a subject, as well as a graph of strain plotted as a function of time. The graph of FIG. 5 also shows tissue expansion and compression during the subject's swallow.

[0038] The many features and advantages of the invention are apparent from the detailed specification, and thus, it is intended by the appended claims to cover all such features and advantages of the invention which fall within the true spirit and scope of the invention.

Further, since numerous modifications and variations will readily occur to those skilled in the art, it is not desired to limit the invention to the exact construction and operation illustrated and described, and accordingly, all suitable modifications and equivalents may be resorted to, falling within the scope of the invention.

Claims

What is claimed is:

1. A method of imaging an event of swallowing of a subject comprising: configuring a magnetic resonance imaging (MRI) machine to take a tagged magnetic resonance image of the subject; indicating for the subject to swallow; triggering the MRI machine to acquire images of the subject during a swallow made by the subject; and synchronizing the indicating for the subject to swallow with the triggering of the MRI machine to acquire images of the subject.

2. The method of claim 1 further comprising indicating for the subject to prepare to swallow by taking a sip of a liquid.

3. The method of claim 2 further comprising the liquid taking the form of a contrast liquid.

4. The method of claim 1 further comprising the indicating to swallow taking the form of a auditory cue.

5. The method of claim 4 where the indicating to swallow takes the form of a double beep.

6. The method of claim 2 further comprising the indicating for the subject to prepare to swallow takes the form of an auditory cue.

7. The method of claim 6 wherein the indicating to prepare to swallow takes the form of a single beep.

8. The method of claim 1 wherein the MRI machine is triggered to acquire images when the subject swallows.

9. The method of claim 1 wherein the subject is imaged during the swallow for 2 seconds.

10. The method of claim 1 wherein the subject engages in a 20 second swallowing cycle, repeatedly swallowing over the 20 second swallowing cycle.

11. A system for imaging an event of swallowing of a subject, comprising: a magnetic resonance imaging machine configured to take a tagged magnetic resonance image of the subject during an event of swallowing; a device for indication configured to play an indication for the subject to swallow; a trigger in communication with the magnetic resonance imaging machine configured to cause the magnetic resonance imaging machine to capture the tagged magnetic resonance image of the subj ect; wherein the indication for the subject to swallow and the trigger are synchronized to capture the tagged magnetic resonance image of the subject during the event of swallowing.

12. The system of claim 11 further comprising a liquid for the subject to swallow.

13. The system of claim 12 further comprising the liquid taking the form of a contrast liquid.

14. The system of claim 11 wherein the device for indication takes the form of an auditory cue.

15. The system of claim 14 wherein the indication takes the form of a double beep.

16. The system of claim 11 wherein the indication comprises a pre-indication indicating that the subject should prepare to swallow.

17. The system of claim 16 wherein the pre-indication comprises a single beep.

18. The system of claim 1 1 wherein the magnetic resonance imaging machine images for a predetermined period of time during the event of swallowing.

19. The system of claim 18 wherein the predetermined period of time is approximately 2 seconds.

20. The system of claim 18 wherein the subject engages in a 20 second swallowing cycle, repeatedly swallowing, while the magnetic resonance imaging machine is synchronously triggered for imaging during an approximately 20 second predetermined period of time for imaging.