Application on Digital Infrared Thermal Imaging Presented by: Rubie F. Viñas, 方如玉 Adviser: Dr. Shih-Chung Chen, 陳世中 LOGO Date: October 16, 2008 Determining Inflammatory State and Follow-up Effect of Methylprednisolone Pulse Therapy in Patients with Graves’ Ophthalmopathy www.themegallery.com Company Logo Abstract What is the aim of this study? Elucidate the feasibility of DITI • Biomedical Field Subjects • Patients with GO Objectives • Determine – Inflammatory state – Follow-up effect of treatment » Methylprednisolone Pulse Therapy www.themegallery.com Company Logo Author T.-C. Chang, Y.-L. Hsiao Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University Address: 7 Chung-Shan South Road, Taipei, Taiwan E-mail: tienchunchang@ntu.edu.tw S.-L. Liao Department of Ophthalmology, National Taiwan University Hospital and College of Medicine, National Taiwan University Address: 7 Chung-Shan South Road, Taipei, Taiwan www.themegallery.com Company Logo Outline I. II. Introduction Patients and Methods A. Patients B. Methods III. Statistical Analysis IV. Results V. Discussion A. Conclusion B. Recommendation www.themegallery.com Company Logo I. Introduction DITI - Digital Infrared Thermal Imaging Diagnostic technique • Non-invasive • No exposure to radiation Applications Evaluation of dry eye in the Ophthalmological field X Evaluation of the Clinical Activity of GO – Monitor the temperature distribution of the human skin www.themegallery.com DITI CAMERA THERMOGRAMS Capture images called thermograms Thermographic Images Company Logo I. Introduction (cont.) Inflammation Latin: Inflamatio English: To set on fire Is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Cause • Local increase in temperature www.themegallery.com Company Logo I. Introduction (cont.) GO - Graves’ Ophthalmopathy • Other Names – Graves' Thyroid-associated – Dysthyroid Orbitopathy – Exophthalmos • Autoimmune inflammatory disorder – Cause » Inflammation of the eyes – Affects » Orbit of the eye, with or without thyroid disorder • Patients Treatment – Use Immunosuppressive Agents » Graves’ Ophthalmopathy is in an inflammatory or so-called active state. www.themegallery.com Company Logo I. Introduction (cont.) To assess the activity of GO 1. CAS - Clinical Activity Score • Origin – Introduced » Mourits – Revised » International Ad Hoc Committee (1992) Classification of eye changes of Graves’ disease. Thyroid 2:235–236 • Measure – One Point » Mild/Severe Conjunctival Injections – Problem 1. Not sensitive enough Detect the effect of treatment clearly 2. Very subjective in nature In the assessment of pain with eye movement – Solution » Objective assessment of disease activity www.themegallery.com Company Logo II. A. Patients and Methods Patients Group I: 1. 14 patients with GO • Gender – – • Mean Age = 39.0±11.4 (standard deviation) – • Age Range 19–55 Mean CAS = 2.5±1.0 ( – 2. 3 men 11 women Range 0–4 16 normal controls • Gender – – • Mean Age = 34.4± 11.6 – 7 men 9 women Age Range 25–65 Methods • GO – – • Orbital computed tomography History of hyperthyroidism CAS – Calculated from seven items with one point given for each item present: 1. Pain with Eye Movement 2. Spontaneous Retrobulbar Pain 3. Eyelid Erythema 4. Eyelid Edema or Swelling 5. Conjunctival Injection 6. Chemosis 7. Caruncle Swelling www.themegallery.com Company Logo II. Patients and Methods (cont.) Group II: 1. 11 patients with GO includes 5 patients from the first group Gender • • 4 men 7 women Mean Age = 47.5±11.0 years (standard deviation) • Age Range 26–60M Mean CAS = 2.8±0.8 • Range 2–4 No history • • Methylprednisolone Pulse Therapy Radiation Therapy of the orbits Method Intravenously infused Methylprednisolone • • Amount 500 mg Frequency daily – 3 Consecutive days Procedure • WHEN Before treatment 24 hour after completion of treatment Measure 1. 2. www.themegallery.com Temperatures and CAS Thermal density plots of the eyes Company Logo II. B. Patients and Methods (cont.) Methods Measure • Local temperatures A. B. C. D. E. F. G. • Instrument – Lateral orbit (reference point) Upper eyelid Caruncle Medial Conjunctiva Lateral Conjunctiva Lower Eyelid Cornea Digital Infrared Thermal Image System » Spectrum 9000 MB Series (United Integrated Service, Taipei Hsien, Taiwan) Room Temperature ~ 23°C. Reference Black Plate • • Reflected the room temperature Place – – • In front of the system Above and Lateral to the eyebrow Purpose – www.themegallery.com Ensure accurate temperature calculation Company Logo II. Patients and Methods (cont.) Reference Plate Ensure accurate temperature calculation Upper Eyelid Reference Point Lateral Orbit Lateral Conjunctiva Caruncle Medial Conjunctiva Cornea Lower Eyelid Filter 1 : Blue Colors Filter 2 : Red Black Temperature Degree : Lowest Highest Bar Length = 1 cm Violet Blue Green Yellow Orange Red Grayish White Histogram Local Temperature Thermal Density Plot www.themegallery.com Company Logo II. 1. Patients and Methods (cont.) System calibration – Each examination – Procedure 1. Place Thermometer Sensor on the focus of measurement target 2. Opening the icon “Fever Test Setup” – FOCUS OPEN ICON “Fever Test Setup” “Thermal Reference Source” will appear 3. Select “Manual” icon 4. Key in temperature value – START From thermometer 5. System in now ready for the patient test MANUAL ICON KEY IN TEMPERATURE VALUE SYSTEM IS NOW READY www.themegallery.com Company Logo II. 2. Patients and Methods (cont.) Check if the Following Rules are Implemented Patients • • • • Not allowed to wear make-up Not allowed to Drink hot or cold water Not allowed to smoke Requirement – Sit in the room and rest for 5 min before the examination. 3. 4. Patient sat before the camera Picture of each eye was captured Left and Right Eye 5. Measure the temperatures of the target areas • Computer 6. Computation A. Difference between Temperature • Lateral Temperature – Target Area www.themegallery.com Company Logo II. Patients and Methods (cont.) B. Coefficient of Variation (CV) A. Intra-assay • • Healthy Person Local Temperature 0.3% (31.6±0.1°C, n=5) – – • Temperature = 31.6°C lateral orbit, reference point 0.7% (33.7±0.2°C) – – Temperature = 33.7°C Caruncle) B. Inter-assay • 2.5% (31.0±0.8°C, n=5) – – • Temperature = 31.0°C lateral orbit, reference point 2.0% (33.6±0.7°C) – – www.themegallery.com Temperature = 33.6°C Caruncle Company Logo II. 7. Assessments DITI and CAS • 8. Masked manner Study Ethical standards • 9. Patients and Methods (cont.) Declaration of Helsinki Informed Consent Obtained from the participants • After explanation of the nature and possible consequences of the study 10. Approval Institutional Review Board of National Taiwan University Hospital www.themegallery.com Company Logo III. Statistical Analysis 1. Temperature Difference Data • Patients VS. Normal Controls – Temperature • Before and After Methylprednisolone Pulse Therapy – 2. 3. Student’s t test Statistically Analyzed » Data failed to pass the normality test Perform Mann–Whitney rank sum test Student’s paired test Analyzed » Data failed to pass the normality test Perform Wilcoxon signed rank test Correlation Coefficient Temperature Variation and Change in Clinical Activity Score • • After Methylprednisolone Pulse Therapy Spearman Rank Order Correlation Analyzed • Calculation Coefficient of Variation Intra-Assay or Inter-Assay – www.themegallery.com (Standard Deviation / Mean) × 100% Company Logo Whole System START SYSTEM CALIBRATION CHECK: RULES ARE IMPLIMENTED POSITION PATIENT TAKE PICTURE: LEFT EYE RIGHT EYE ASSESSMENT STUDY INFORMED CONSENT APPROVAL END SOFTWARE: MEASURE TEMPERATURE OF TARGET AREAS STATISTICAL ANALYSIS: TEMPERATURE DIFFERENCE CORRELATION COEFFICIENT COEFFICIENT OF VARIATOIN www.themegallery.com Company Logo IV. Difference Temperature • Patient Parts – – – – www.themegallery.com Caruncle Medial Conjunctiva Lateral Conjunctiva Lower Eyelid Results Statistically significantly Higher than those of normal controls No Difference Temperature • Patient Parts – – – Upper Eyelid Cornea Lateral Orbit (reference point) Patients and Normal Controls Data are presented as mean ± standard deviation *p<0.05 vs. normal controls Company Logo IV. Results (cont.) 11 GO patients Treatment • Methylprednisolone Pulse Therapy Temperatures • Parts – – – • Significantly decreased after treatment Sum of the Temperatures • Parts – – – – – – • 201.9±7.0°C vs. 196.9±9.2°C, p<0.05 CAS • Significantly decreased after Methylprednisolone Pulse Therapy. – Upper Eyelid Caruncle Medial Conjunctiva Lateral Conjunctiva Lower Eyelid Cornea Significantly decreased after treatment – Caruncle Medial Conjunctiva Lower Eyelid 2.8±0.8 2.2±1.0 (p<0.05) Difference • • Sum of the Temperatures before and after treatment Significantly and Positively correlated – Change in clinical activity score (correlation coefficient=0.8, n=22, p=0.000). www.themegallery.com Company Logo IV. Results (cont.) Data are presented as mean ± standard deviation Lateral orbit is a reference point *p<0.05 vs. after treatment www.themegallery.com Company Logo IV. Results (cont.) METHYLPREDNISOLONE PULSE THERAPY Patient with GO BEFORE NORMAL CONTROL AFTER Thermal Density Plots of the Right Eye Notes: Conditions of the filters are the same for these three pictures. Bar length=1 cm www.themegallery.com Company Logo IV. Results (cont.) METHYLPREDNISOLONE PULSE THERAPY Patient with GO BEFORE AFTER Thermal Density Plots of the Left Eye Notes: Conditions of the filters are the same for these three pictures. Bar length=1 cm www.themegallery.com Company Logo V. Discussion Study DITI • Objectively Measure Temperature – Patients with GO » Various areas of the eyes » Adnexa – Reflecting the degree of inflammation • Thermal Density Plot – Clearly shows which area of the eye has most severe inflammation. • Follow-up the Effects – Methylprednisolone Pulse Therapy www.themegallery.com Company Logo V. Discussion (cont.) Study Comparison • Sum – Local Temperatures of various areas of the eye – Thermal density plots before and after treatment • Indicate – Condition of GO is improved after Methylprednisolone Pulse Therapy. – Change in temperature Well correlated with the change in CAS. » Decreased temperature was caused by a decrease in CAS » Improvement in inflammation of GO Detect change in inflammation Show detailed improvement of inflammatory signs • Eyes of patients with GO www.themegallery.com Company Logo V. Temperature Highest Caruncle Lowest Cornea Why? Cornea is Vascular Discussion (cont.) Cornea Caruncle • During inflammation – Significant differences are more easily seen in the caruncle than in the cornea www.themegallery.com Company Logo V. Discussion (cont.) DITI - Digital Infrared Thermal Imaging Non-invasive examination that is already used • Rheumatological field Recent Studies Temperature differences between the hands in complex regional pain syndrome patients increased significantly when the sympathetic system was provoked Temperature changes in the plantar surface correlated with lower back pain intensity Relationship between plantar skin temperature and diabetic neuropathy, • Identifying small fiber neuropathy Identify Breast Cancer • Heat generated Angiogenesis www.themegallery.com Company Logo V. Discussion (cont.) Present Study DITI – Objectively determine clinical activity and effect of Methylprednisolone Pulse Therapy in patients with GO. » Depends on the heat generated in the inflammation of GO www.themegallery.com Company Logo V. Discussion (cont.) Conclusion Digital Infrared Thermal Imaging • Evaluate the inflammatory state of GO • Follow-up Effect – Methylprednisolone Pulse Therapy Recommendation A large scale study and further research are therefore merited www.themegallery.com Company Logo Reference 1. 2. 3. 4. 5. 6. 7. 8. 9. Jiang LJ, Ng EY, Yeo AC, Wu S, Pan F, Yau WY, Chen JH, Yang Y (2005) A perspective on medical infrared imaging. J Med Eng Technol 29:257–267 Jones BF (1998) A reappraisal of the use of infrared thermal image analysis in medicine. IEEE Trans Med Imaging 17:1019–1027 Prabhakar BS, Bahn RS, Smith TJ (2003) Current perspective on the pathogenesis of Graves’ disease and ophthalmopathy. Endocr Rev 24:802–835 Marcocci C, Bartalena L, Marinò M, Rocchi R, Mazzi B, Menconi F, Morbito E, Pinchera A (2002) Current medical management of Graves ophthalmopathy. 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