It doesn't use X-rays (radiation). Click the icon link on the far left on the upper part of the screen. 6 , 7 , 8 A common MRS finding in malignant gliomas is increased choline and decreased NAA and creatine concentrations compared with normal brain tissue. The next screen will show you three planes. The course begins at 9.30am on Monday 17 October 2022, and finishes late afternoon on Wednesday 19 October 2022. The objective of this protocol is to allow investigators to perform initial test evaluation in humans of new MRI acquisition techniques. FEMALE PELVIS FAST BRACHYTHERAPY PLANNING WO, FEMALE PELVIS CERVICAL CANCER STAGING W/WO, FEMALE PELVIS UTERINE CANCER STAGING W/WO, MR Breast Biopsy - Protocol for Technologists, MR Breast Biopsy - Post & Pillar Biopsy Method, pediatric patients are underPediatric Protocols, PELVIS SACROILIITIS / SI JOINTS / SACRUMWO OR WWO, STEREOTACTIC BRAIN WO, W/WO OR W/CONTRAST, MULTIPLE SCLEROSIS / CORD LESION - CERVICAL SPINE WWO, MULTIPLE SCLEROSIS / CORD LESION - CERVICAL SPINE WO, MULTIPLE SCLEROSIS / CORD LESION - THORACIC SPINE WO, MULTIPLE SCLEROSIS / CORD LESION - THORACIC SPINE WWO, ED CORD/CAUDA IMPINGEMENT SCREENING - TOTAL SPINE WO, MULTIPLE SCLEROSIS / CORD LESION - TOTAL SPINE WWO, MULTIPLE SCLEROSIS / CORD LESION - TOTAL SPINE WO, SPINAL VASCULAR MALFORMATION - MRA/MRI TOTAL SPINE WWO, MRA LOWER EXTREMITY BILATERAL (RUN-OFF) W/WO. The following spectral changes are common in brain tumor MRS (Fig. How can MRI spectroscopy indicate underlying disease? MR Bilateral Breasts WWO ProtocolMR ISPY Breast ProtocolMR Breast Biopsy - Protocol for TechnologistsMR Breast Biopsy - Post & Pillar Biopsy MethodMR Breast - Guided Wire Localization. Prediction of IDH Status Through MRI Features and Enlightened Reflection on the Delineation of Target Volume in Low-Grade Gliomas. Neuroradiologyprotocolscurrently applied in our MRI section. All MRI CE courses are also accepted by the ARMRIT. Localized proton MR spectroscopy (MRS) of the human brain, first reported more than 20 years ago,(1-3) is a mature methodology that is used clinically in many medical centers worldwide for the evaluation of brain tumors. Try. Introduction and overview. used for biomedical NMR spectroscopy applications since the 1980s. 2006 Nov;16(4):605-18, viii. such as tubular retractors and Raman spectroscopy, which allow surgeons to access deep . Hardware doesn't necessarily mean you have to change the protocol. Combined MRI and proton MRS led to a 15.4% greater number of correct If infection/osteo is a diagnostic consideration, please run. Scan Notes: The radiologist will plan the spect voxels. MSK protocolscurrently applied in our MRI section. Main components contributing to the signal, N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), Marker for neuronal integrity and function, osmolyte, metabolic precursor, Choline (Cho), phosphorylcholine (PC), glycerophosphorylcholine (GPC), Very low detectable concentrations in normal tissue, Pathologically altered cells and cerebrospinal fluid. Altered metabolism is a hallmark of cancer, which has been recognized as an important mechanism and biomarker for cancer. Clipboard, Search History, and several other advanced features are temporarily unavailable. Last updated:3/21/2019 16 In addition they found that the Gly:Myo ratio did distinguish GBM from metastases and low-grade astrocytomas, suggesting that Gly might be a useful biomarker for tumor characterization. Click on "LongTeBrain" and then click "OK" Choose "Spectrum Phase Adjustment" so the checkmark is visible in the box. as seen in magnetic resonance imaging, effects such as J-modulation or the transfer of magnetization after selective excitation of particular spectral lines can affect the relative strengths of spectral lines. Epub 2006 May 15. 2022 Jan 27;4(1):vdac006. It is based on sophisticated technology that excites and detects the change in the direction of the rotational axis of protons found in the water that makes up living tissues. Radiologistsworkclosely with OHSU MRI techs in the art of creating optimal images from current technology. Typically they will want one on whatever lesion they are looking at, and one in normal healthy white matter. It can help determine the specifics of a tumor, such as a tumor's aggressiveness, or tumor metabolism. The pediatric radiologists will usually protocol specific sequences they need in RIS. Either ratios normalizing the individual metabolites to the creatine signal (e.g., NAA:Cr) are used or the metabolites are directly compared to each other (e.g., NAA:Cho). Magnetic resonance spectroscopy (MRS) is a proven and useful method for the evaluation, assessment of severity, therapeutic planning, posttherapeutic monitoring, and follow-up of diseases of the brain and other regions of the body . An MRI Spectroscopy is often done to diagnose certain metabolic disorders, including those affecting the brain. ISTAT values can be used for subsequent scans out to the 6-month limit. Still, despite a considerable volume of research in the field, no consensus exists regarding the use of normalized versus nonnormalized ratios or quantitative data, the specificity and sensitivity of the method, or the true value of the method in clinical decision making. sharing sensitive information, make sure youre on a federal This is useful in differentiating normal brain tissue from tumor, regions with ischemia, or other tissue abnormalities. 11.1b,c), whereas multiple smaller voxels (multivoxel MRS or chemical shift imaging [CSI]) in one or several slices (single-slice two-dimensional chemical shift imaging [2D CSI]; multislice three-dimensional CSI [3D CSI]) are used to characterize the metabolic profile over different parts of a heterogeneous tumor and/or surrounding tissue (Fig. Right mouse click on the spect and choose "Spectroview" sequence Click the icon link on the far left on the upper part of the screen. It includes how the exam works, how it is done, how to prepare for the exam, what to expect during the exam, and how to get exam results. Protocols listed have been reviewed and approved by a radiologist. . MRS has potential to improve diagnosis and treatment monitoring of childhood brain tumours and other CNS diseases, facilitate biopsy and surgical planning, and provide prognostic biomarkers. MRS can do rather than what MRS is. Proton spectroscopy is easier to perform and provides much higher signal-to-noise than either sodium or phosphorus. Atoms with an odd mass number such as 1 H, 31 P and 13 C possess the quantum property of "spin" and behave as dipoles aligning along the axis of an applied magnetic field. A single voxel (single voxel spectroscopy [SVS]) with a usual voxel size of 3 to 8 cm3 is preferably used to characterize the metabolic profile of a rather homogeneous solid or cystic part in a tumor (Fig. Contrast enhancement on postcontrast T1-weighted images is one of the most common methods for assessing glioma grade. Basically, three different categories of clinical PET/MRI hardware can be distinguished: (1) separate gantries in different rooms [ 56 ], (2) co-planar concepts where scanner gantries are in the same room and connected by a patient handling system, i.e., patient couch on rails [ 19 ], and (3) fully integrated systems [ 57 ]. Abstract. 11.3): (1) decrease of NAA as a marker for a decreased number of neurons or neuronal function per volume as seen not only in the tumor itself but also in the surrounding edema; (2) increase of choline as a marker of increased cell membrane turnover, which might reflect tumor growth, tumor necrosis, or gliosis; (3) increase of lactate and or lipids mainly as a marker of tumor necrosis, which is not only related to treatment response but is also a natural feature in viable tumor with energy requirements exceeding energy supply; and (4) decrease of all metabolites as a marker of general cell destruction and general decrease of molecules contributing to the spectrum. 2019 Jun;20(6):967-975. doi: 10.3348/kjr.2018.0690. Zeinali-Rafsanjani B, Mosleh-Shirazi MA, Faghihi R, Saeedi-Moghadam M, Lotfi M, Jalli R. Br J Radiol. 2019 Dec;92(1104):20190216. doi: 10.1259/bjr.20190216. Consequently, the use of 3 T MRI for radiosurgery planning is highly desired. 11.1bf). For spiral or irregular k-space sampling, the approach is to first re-grid the k-space data onto a rectangular array ( 59 - 61 ). The aim of the study was to see if the use of MR spectroscopic imaging (MRSI) along with functional MRI (fMRI) can better define both the target and the critical structures to be avoided to improve radiation delivery in gliomas. MRS physics have been described extensively in several textbooks, 2 and only some basics need to be discussed here for the understanding of methodological challenges related to the clinical interpretation of data acquired. Be sure to select the appropriate box in EPIC if the exam is not to be read by a radiologist. Furthermore, tissue inhomogeneity within the voxelnot only due to partial volume effects of, for example, cerebrospinal fluid (CSF), but also tumor inhomogeneitiesneeds to be taken into account. In this context it is important to emphasize the need to review conventional MR images prior to voxel/region of interest (ROI) positioning to define the area of the lesion that is most interesting for MRS and relevant for the clinical question to be answered. MR spectroscopy provides a measure of brain chemistry.The most common nuclei that are used are 1H (proton), 23Na (sodium), 31P (phosphorus). Any electrically, magnetically or mechanically activated implant (e.g. About Press Copyright Contact us Creators Advertise Developers Terms Privacy Policy & Safety How YouTube works Test new features Press Copyright Contact us Creators . Exam Preparation Advanced MRI Tools With Many Applications in Brain Imaging Diagnosing tumors and other brain diseases and conditions can be a complex undertaking. 11.4 illustrates a WHO grade III oligodendroglioma with highly increased Cho and decreased NAA. An intensity-modulated radiation therapy (IMRT) plan was developed using the dose constraints based on both the anatomical and the functionally critical regions. FOIA In 2003, Paul C. Lauterbur and Sir Peter Mansfield were awarded the Nobel Prize in Medicine for their discoveries concerning magnetic resonance imaging. In vivo magnetic resonance spectroscopy provides insight into metabolism in the human body. There are three techniques in wide use to derive one or more perfusion values: techniques dynamic susceptibility contrast (DSC) MR perfusion dynamic contrast enhanced (DCE) MR perfusion arterial spin labeling (ASL) MR perfusion derived values time to peak (TTP) mean transit time (MTT) cerebral blood volume (CBV) cerebral blood flow (CBF) Charge as: Usually added on to a Neuro Brain exam. doi: 10.1093/noajnl/vdac006. Radiologistsworkclosely with OHSU MRI techs in the art of creating optimal images from current technology. Intermediate echo times are used to more clearly depict lactate because the resonance inverts in the spectrum and points below the baseline, and to assure lesser relaxation effects on the main metabolites NAA, Cho, and Cr compared to long echo times. Voxel position should be illustrated to the reader of the spectrum with reference images (Fig. Kwock. Technol Cancer Res Treat. [Application of (1)H MR spectroscopic imaging in radiation oncology: choline as a marker for determining the relative probability of tumor progression after radiation of glial brain tumors]. The spectroscopic metabolic cartography is produced on an axial plane. Dr. Alice Fung has approved the protocols below. It is clear that the contrast enhancement does not necessarily correspond to the regions of high choline concentration because elevated choline levels have been found beyond the contrast-enhancing tumor area or, in cases of no enhancement, in areas with hyperintense signal on T2-weighted and fluid-attenuation inversion recovery (FLAIR) images representing tumor. No correlation between MRSI based Cho:Cr > or =2 and MR defined CTV nor their location was noted. This is important because MRS is not available on all clinical MRI systems. MRI uses a large magnet, radio waves and a computer to produce these detailed images. Ding H, Huang Y, Li Z, Li S, Chen Q, Xie C, Zhong Y. Technol Cancer Res Treat. and transmitted securely. Connectomes and Functional Pathway Maps for Surgical Planning. Center for Magnetic Resonance Imaging & Spectroscopy HUP Clinical Research Staff using contrast agents during your MRI Research Scan - February 2021. View our list of machines available for research. Coil: Head. 7 , 9 , 10 , 11 Indication of malignant transformation and early progression of initial low-grade gliomas is the increase in the creatine concentration and progressive decrease in NAA and myoinositol concentrations and increased choline concentration. Magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion-weighted imaging (DWI) are the most extensively used for enabling lesional characterization of different brain disorders. government site. Dydak and Schar. Magnetic Resonance Imaging. 1/12/2021: Urgent note fortechnologists: for pre-op stereotactic and stealth exams with motion,notifyNavTeam@ohsu.eduof the issue. Before When looking at an isolated voxel metabolite ratio, such as Cho:NAA, the problem arises of not knowing whether the abnormality causing an observed spectral change is in the numerator or in the denominator. One set is based on conventional multislice (2D) or 3D methods, a second set is based on the new simultaneous multislice (SMS) protocols (also called mux or multiband), and a third set are some special methods (spectroscopy and qMRI). Do not click any other options. The aim of this chapter is to provide a comprehensive introduction to the new possibilities that. MeSH Magnetic resonance imaging (MRI) uses radio waves and strong magnets to take pictures of the organs and tissues of the body. Furthermore spectral patterns of primary pediatric and adult intracranial tumors and secondary tumors are presented, and the findings in some common differential diagnoses are described. Image-fusion of MR spectroscopic images for treatment planning of gliomas. A more robust and clinically often more feasible method of data interpretation is a semiquantitative approach with calculation or visual appreciation of metabolite ratios. A broad spectrum of non-neoplastic lesions can radiologically mimic cerebral neoplasms. Because MRI doesn't use X-rays or other radiation, it's the imaging test of . Conventional MRI is limited in its ability to reliably grade gliomas. Do not click any other options. Magnetic resonance imaging, or MRI, uses strong magnetic fields and radio waves to produce detailed images of the inside of the body. Magnetic resonance imaging (MRI) is a medical imaging technique used to produce high quality images of the human body. Equipped with these technologies and a very strong global collaboration network, we enable you to lead in MRI. Our innovative MRI technologies offer you exceptional image quality, efficiency, and speed, while providing patient friendliness and investment protection. We guarantee that all of the MRI CE credits you earn will be accepted by state registries in the USA and Canadian territories for all licensed radiologic technologists, as well as for ARRT renewal. The metabolic data from the high-resolution 2HG map should be highly valuable for treatment planning and posttreatment monitoring. In setting position, midline posterior approach with reflection of . cAlthough stimulated echo acquisition mode (STEAM) earlier was often preferred, especially for SVS because it allowed for more precise slice selection and usage of shorter TE, point resolved spectroscopy (PRESS) is now the clinical method of choice because earlier technical problems have been overcome, and the method allows for twice the signal-to-noise ratio compared to STEAM. It's generally used to diagnose abdominal pain. Ramesh K, Mellon EA, Gurbani SS, Weinberg BD, Schreibmann E, Sheriff SA, Goryawala M, de le Fuente M, Eaton BR, Zhong J, Voloschin AD, Sengupta S, Dunbar EM, Holdhoff M, Barker PB, Maudsley AA, Kleinberg LR, Shim H, Shu HG. APPENDICITIS WO- Updated 1/13/2022ABDOMEN WOor W/WOABDOMEN/PELVIS ROUTINE WOABDOMEN/PELVIS ROUTINE W/WOENTEROGRAPHY W/WO- Updated 1/13/2022LIVER MASS W/WOLIVER MASS with MRCP WOLIVERMASS with MRCP W/WOMRCP WOPANCREAS W/WOwith MRCPPANCREAS W/WO with MRCP and SECRETINRENAL MASS W/WORENAL ARTERY STENOSIS W/WOSCROTUM WO or W/WO- Updated 1/13/2022 Magnetic Resonance Imaging and Spectroscopy. MR spectroscopy analyzes molecules such as hydrogen ions or protons. MRS is employed as a research tool outside the brain in liver disease and disorders of muscle metabolism. This will enable noninvasive monitoring of the effects of interventions such as weight loss or pharmacotherapy in patients with fatty liver diseases. 31 terms. Make every effort possible toavoid placing any part of the voxelss inside CSF, bone, or air. 230 0 obj
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Despite some controversy the clinical potential for MRS in brain tumor workup is well documented. Lower extremities NOT listed below: use adult protocols with FOV/Slice/Gap adjustments for patient size. 8600 Rockville Pike Magnetic Resonance Imaging (MRI) is a medical imaging procedure for making images of the internal structures of the body. OHSU is an equal opportunity affirmative action institution. MR spectroscopy gives a chemical profile of a region of brain. Scanner preference: 3T only All pulse sequences, including the ones that we testing, can be used on FDA-approved MRI scanners as long as they meet FDA guidelines for non-significant risk, and our new sequences all meet these guidelines. The chapter is focused on the use of MRS as a complement to conventional MR imaging (MRI) in daily clinical practice and not as a scientific research tool. For all Pelvic MRI studies except the Bladder Protocol or the MR Urogram:Please have the patient void their bladder prior to exam to improve image quality. endstream
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Magnetic Resonance Imaging. Use of the latter usually generates spectra of high quality, however, including a more limited number of metabolites compared to short echo time spectra. Provisional lecture list Basis of NMR Relaxation Parameters and Spin Echoes Short echo times allow for evaluation of metabolites with short relaxation times (e.g., myoinositol). Key features Course description CQR distribution A Phase I IMRT dose intensification trial in gliomas using this information is planned. Magnetic resonance spectroscopy forms a part of diagnostic sequences used for imaging brain infections. MRI & Spectroscopy JOB DETAILS Salary Range $58,000 - $94,000 Recommended High School Courses n/a Magnetic resonance imaging (MRI) uses magnetism, radio waves and computers to acquire medical images. Processing pipelines must also be developed to use these data optimally. 3-5 While initial diagnosis is . () While there have been studies of human brain tumors using heteronuclei such as phosphorus (31 P) and sodium (11 Na),(5,6) by far the most spectroscopy . Focus will be on what. marciat0109. When conventional imaging by magnetic resonance imaging (MRI) or computed tomography (CT) provides limited . Dr. David Petterssonhas approved the protocols below. Lichy MP, Bachert P, Hamprecht F, Weber MA, Debus J, Schulz-Ertner D, Schlemmer HP, Kauczor HU. It outlines all sequences and protocols currently applied in our MRI section. 2014 Jan;33(1):16-24. doi: 10.5732/cjc.013.10217. Of these mainly phase correction might need some manual adjustment as illustrated in Fig. It is useful to run an additional COR T2 to help plan the voxels. Single-voxel MRS shows a decrease in N-acetylaspartate in the left temporal compared to the right lobe. Fig. All MSK protocols for pediatric patients are underPediatric Protocols. There were 53.4% of the examined neonates in the weight group ranging from 2 to < 3 kg. 2006 May;16(2):269-83, x. Mullins. 13 The presence of lipid or lactate on MRS is highly suggestive of higher-grade malignant gliomas mainly seen in grade IV gliomas but not correlated to the degree of tumor infiltration. 11.1df). Our radiologists workclosely with OHSU MRI technologistsin the art of creating optimal images using current technology. Compared to the wide variety of available sequences and parameters in MRI the choice of MRS sequences can be standardized regarding sequence type and acquisition parameters in a very robust way to allow for comparable data not only within one patient but within larger clinical populations (Table 11.2). (e.g., Certificate of Coverage (COC) or Summary Plan Description (SPD) and Medicaid State Contracts) may differ greatly from the standard benefit plans upon which this Medical Policy . Spectroscopy is a series of tests that are added to the MRI scan of your brain or spine to measure the chemical metabolism of a suspected tumor. 2005 May 1;62(1):20-31. doi: 10.1016/j.ijrobp.2004.09.027. 1, 2 In the particular case of glioblastoma (GBM) there is significant alteration in the metabolic profile compared to the healthy brain tissue that can be detected in patients using in vivo magnetic resonance spectroscopy. 12 patients with gliomas underwent multivoxel MRS and functional imaging using GE processing software. An official website of the United States government. If you are considering bringing an MRI system into your radiation oncology department or you need to adapt your diagnostic radiology MRI systems for RT planning, the Acquired MRS raw data need to be postprocessed with software provided by the manufacturers or with postprocessing tools such as LCModel (LCMODEL, Inc. Oakville, Ontario, Canada). Longitudinal multivoxel MR spectroscopy study of pediatric diffuse brainstem gliomas treated with radiotherapy. Magnetic Resonance Imaging (MRI) is a non-invasive imaging technology that produces three dimensional detailed anatomical images. Keywords: cancer, imaging, lymph node, MRI, nasopharynx MR spectroscopy 1. Role of MRI-Based Functional Imaging in Improving the Therapeutic Index of Radiotherapy in Cancer Treatment. Each exam takes about 45 minutes of scanning. Rofo. Bethesda, MD 20894, Web Policies Cho/Cr ratio map generated from 3D CSI measurement: Spectral nap generated from 3D CSI measurement . official website and that any information you provide is encrypted 11.5f,g). Click on "LongTeBrain" and then click "OK". T2WD bZr~|N 0ZRPF)qk`S. Routine anatomical imaging with CT and MRI does not reliably indicate the true extent or the most malignant areas of gliomas and cannot identify the functionally critical parts of the brain. 12 Significantly increased Cho:Cr and Cho:NAA ratios are usually seen in high-grade tumors compared to less increased Cho:Cr or decreased NAA:Cr in low-grade tumors compared to normal brain tissue. Subsequently, voxel position should be related to morphological findings to establish the clinical question to be answered with the spectra from each voxel. Introduction. Telephone(718) 428-1500 Email[email protected] LocationsLocations MR PERFUSION SPECTROSCOPY Specialized MRI techniques that help diagnosing brain tumors and other conditions. Terminology that eliminates "nuclear" reflects that neither "radioactive nuclei" nor "radiation" are parts of clinical MRS studies. Oregon Health & Science University is dedicated to improving the health and quality of life for all Oregonians through excellence, innovation and leadership in health care, education and research. Current fitting software is either targeted at general spectroscopy fitting, or for specific protocols. Imaging can detect effect of radiation on surrounding structures. Magnetic Resonance. Int J Radiat Oncol Biol Phys. Magnetic resonance imaging (MRI) is a diagnostic procedure that uses a combination of a large magnet, radiofrequencies, and a computer to produce detailed images of organs and structures within the body. The transition between images is made on the vertical Z plane. ANY INFECTION/OSTEO CASE REGARDLESS OF BODY PART: nL#n.s'\[LznU ]S~ ~ . . When evaluating the spectral patterns the reader needs to keep in mind spectral changes in metabolite concentrations related to age, which is primarily of interest in neonates and infants, who show increasing NAA concentrations parallel to decreasing choline concentrations with increasing age. The https:// ensures that you are connecting to the The age at the time of MRI examination was ranging from 6 to 60 day (median, 23 days). ABDOMEN and PELVIS W/WOABDOMEN/PELVIS APPENDICITIS WOADRENAL MASS W/WO, FEMALE PELVISBRACHYTHERAPY PLANNING WWO- updated 5/11/2022FEMALE PELVIS FAST BRACHYTHERAPY PLANNING WO - updated 5/11/2022FEMALE PELVIS CERVICAL CANCER STAGING W/WOFEMALE PELVIS FOR ENDOMETRIOSIS W/WO - updated 3/25/2021FEMALE PELVIS UTERINE CANCER STAGING W/WOFEMALE PELVIS / SOFT TISSUE PELVIS W/WO- updated 9/8/20FEMALE PELVIS UAE W/WO, LIVER MASS W/WOLIVER MASS WO & MRCPLIVER MASS W/WO & MRCP with EOVISTLIVER MASS W/WO & MRCPLIVER MASS W/WO EOVISTLIVER MASS WO IRON (Fe) QUANTIFICATIONLIVER MASS W/WO IRON (Fe) QUANTIFICATIONPANCREAS W/WO MRCPPANCREAS W/WO SECRETINPELVIMETRY WOPERIANAL FISTULA W/WO-Updated 10/12/2021PLACENTA WOPROSTATE W/WORECTUM/RECTAL CA W/WO-Updated 9/20/2021RENAL DONOR W/WO-Added6/13/2022RENAL MASS W/WORENAL ARTERIAL SCLEROSIS W/WOSCROTUM W/WOUROGRAM W/WO. The Therapeutic Index of radiotherapy in cancer treatment oligodendroglioma with highly increased Cho and decreased NAA 33 ( 1:16-24.! 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The objective of this protocol is to provide a comprehensive introduction to the right lobe official website that... Applied in our MRI section values can be used for biomedical NMR spectroscopy applications since the 1980s the Therapeutic of! Wednesday 19 October 2022, and several other advanced features are temporarily unavailable,... Quality, efficiency, and speed, while providing patient friendliness and investment.... Spectroscopy provides insight into metabolism in the left temporal compared to the right lobe metabolism is hallmark... Of the inside of the organs and tissues of the spectrum with reference images ( Fig position, midline approach. To change the protocol ( MRI ) is a diagnostic consideration, please run a diagnostic consideration please... 2019 Dec ; 92 ( 1104 ):20190216. doi: 10.5732/cjc.013.10217 approved a! 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