Near Infrared Spectroscopy NIRS Technology Update James E

Near Infrared Spectroscopy (NIRS): Technology Update James E. Muller, MD Chief Medical Officer Infraredx, Inc.

James E. Muller, MD §Salary: §Infra. Re. Dx, Inc. My presentation will include off label discussions: Use of NIR to identify plaques at risk of causing MI when dilated, and other uses

A B IVUS Transducer C D pre E Post-stenting NIR Mirror NIR - Lipid Core IVUS - Structural Image Schulz et al. JACC 2009

NIR and IVUS NIR Ø Tissue diagnosis available in the cath lab 4

Combination NIR and IVUS Imaging System 3. 2 Fr Intracoronary catheter Console containing NIR laser and algorithms FDA cleared and CE Mark In use in over 20 hospitals Over 2, 000 patients have had NIR scans

Chemogram of RCA with ring LCP at stenosis in 62 yo male Stenosis Similar chemogram with ring LCP from autopsy specimen of 48 yo male Massive LCP and remnant of fatal thrombus Distal embolization following dilation leading to MI and CPR Sudden Coronary Death Thrombus remnant

A Rotation (°) Simultaneous IVUS and NIR Imaging of a Coronary Autopsy Specimen B 60 50 40 30 20 Pullback (mm) 10 NIR Indicates Fibrous Plaque at A and Lipid Core at B Transverse IVUS Images Show Calcification and Suggest Attenuated Plaque Histology Confirms Calcified Fibrous Plaque at A And Lipid Core Plaque at B Data on File. Infra. Re. Dx, Inc. 0

Use of NIRS to Identify Cap Thickness Sean Madden Ph. D and Joel Raichlen, MD Spectra acquired at discrete pullback and rotation positions Spectra transformed into posterior probability of thin cap presence 0 1 Probability mapped to a color R Pixels formed into an image G B

COLOR Registry • 1000 patients - PCI and NIR at baseline • Patients followed for 2 years to identify stenting complications and new coronary events • Launched Jan 2009 • ~20 sites, over 1, 000 patients • Patients now reaching 2 yr FU 9

COLOR Enrollment and Follow-up 1, 000 Patients In data base 4 Nov 2011 10

Red Chemogram With Angiographic Follow-up 1 Post Stent 4 Day 0 Post Stent Day 171 Day 0 2 Day 0 Day 238 5 Day 42 Day 0 Day 316 Post Stent Pre Stent 3 Day 0 6 Day 0 Day 127 Post Stent Pre Stent Day 168

End of LAD stent lands in a lipid core Day 241: --Stenosis at proximal edge of proximal stent 10 cases of restenosis in COLOR Registry. In 9 of those, the stent ended in a lipid core. 12

Temporal Features of LCP Day 730 623 607 600 371 365 305 286 270 238 180 266 235 168 77 84 69 60 229 56 53 30 0 LAD LCX RCA LAD LAD LAD RCA

Chemogram of Ulcerated Lesion 1) Chemogram demonstrates a circumferential LCP at site of ulceration. Courtesy Dr. David Rizik Day 0 Confidential 14

Containment of LCP behind Stent Re-Image: 1) Chemogram Pre Stent Post Stent Day 0 Lipid Core contained behind stent struts Day 0 Confidential Courtesy Dr. David Rizik 15

Day 580 post LAD stent over LCP Day 0 – post stent Day 580 Confidential Courtesy Dr. David Rizik 16

Blinded chemograms 1 year apart IBIS 3 Study Courtesy Dr. Patrick Serruys

Current Status of Intracoronary NIR-IVUS • The technology identifies coronary lipids in a rapid, automated and accurate manner and gives IVUS data. • Lipid core plaques complicate stenting. • Long-term outcomes studies are in progress. • A new technique is available for evaluation of novel anti-athero and anti-thrombotic pharmaceutical agents.