Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Slide 34Slide 35Slide 36Slide 37Slide 38Slide 39Slide 40Slide 41Slide 42Slide 43Slide 44Slide 45Slide 46Slide 47Slide 48Slide 49Cerebral MR Perfusion Imaging2006A. G. Sorensen MDMGH-HST Center for Biomarkers in ImagingA. A. Martinos Center Massachusetts General HospitalHarvard Medical School & Massachusetts Institute of Technology Division of Health Sciences and TechnologyWhy Perfusion With MRI?•A number of neurological illnesses can be traced to abnormal blood flow–Ischemic Stroke–Cerebral Neoplasia–Many, many others, from Alzheimer’s to MS•MRI is heavily used already•It works!Tracer Measurement over timeDynamic DSC Perfusion DataSecondsQuickTime™ and aVideo decompressorare needed to see this picture.DWI / PWI mismatch vs. Final Infarct 4 hr, DWI 4 hr, rCBV 4 hr, rCBF 17 days, T2 4 hr, MTTTime = BrainBetter outcomes with earlier treatmentMeta-analysis of 6 trials, 2775 patientsLancet 2004 363:768Diffusion and Perfusion in Stroke•DWI is now widely used•PWI is in increasing use–No approved contrast agent–Most use some sort of timing map (e.g., time to peak)–ASL continues its testing / development•Desmoteplase or other innovations suggest MRI use may become more widespreadInitial core ?= DWI LesionOr maybe CT edema?Follow-up Infarct(can be variable)Initial PWI LesionThe so-called ‘ischemic penumbra’ -- now accepted (too widely?)MGH / AGSMTT ≠ Tissue at RiskN= 90 Schaefer et al AJNR• DWI is core, but PWI not penumbra when PET is used. Heiss et al Stroke 2004 35(11 Suppl 1)2671Problems (and Potential Solutions)•Monitoring Treatment?•Closing the gap between imaging and clinical outcome–Location matters! •MTT as currently calculated may be overestimating due to delay–Choice of AIF? (delay, dispersion)–New CBF approaches: Local AIF, circular deconvolution•Other markers besides perfusion–Microvascular status–Vasomotion•Imaging Time: still too much time in the scannerMonitoring Treatment with Diffusion / Perfusion MRI•A number of clinical trials have DWI/PWI now as endpoints•One new treatment: hyperoxia for ischemic stroke•Evidence that treatment with 100% oxygen at room pressure widens the therapeutic windowExample: NBO attenuates DWI abnormalities72-yr woman with right MCA stroke, treated with NBODWIMTTDWIMTTDWIMTTBaseline (13 hrs after onset)Large DWI lesionLarger MTT lesionRMCA occlusionDuring NBO (after 4 hrs)DWI lesion smaller (arrows)Stable MTTStable RMCA occlusionPost-treatment (after 24 hrs)DWI lesion growing MTT smallerStable RMCA occlusionSinghal et al MGHNBO: mostly transient effects! DWI rCBV MTT Risk 3 monthNo NBONBONBO Treated = Control = N=16Singhal et al, Stroke 2005Problems (and Potential Solutions)•Monitoring Treatment?•Closing the gap between imaging and clinical outcome–Location matters! •MTT as currently calculated may be overestimating due to delay–Choice of AIF? (delay, dispersion)–New CBF approaches: Local AIF, circular deconvolution•Other markers besides perfusion–Microvascular status–Vasomotion•Imaging Time: still too much time in the scanner•RANTTAS (Stroke 1999 30:293-298):•ASPECTS (Lancet 2000 355:1670): r=0.56Lesion Size Alone Correlates ModeratelyWhy doesn’t imaging better predict / improve outcome?•Specificity of techniques– Not all lesions are equal•The Real Estate factor:–Location–Location–LocationThis is in part because location matters… Day 8 NIHSS = 11Volume ~ 2 cm3Day 8 NIHSS = 2Volume ~ 2 cm3R=0.530510152025300 5 10 15 20 25Measured NIHSS ScoreVolume Scores (Predictions)R=0.820510152025300 5 10 15 20 25Measured NIHSS ScoreHybrid Atlas Scores (Predictions)Menezes / Ay / Martinos - MGH -HSTAtlas-based approach markedly improves imaging-based predictions of outcome (n=46, p<0.01)Problems (and Potential Solutions)•Monitoring Treatment? •Closing the gap between imaging and clinical outcome–Location matters! •MTT as currently calculated may be overestimating due to delay–Choice of AIF? (delay, dispersion)–New CBF approaches: Local AIF, circular deconvolution•Other markers besides perfusion–Microvascular status–Vasomotion•Imaging Time: still too much time in the scannerGlobal versus local AIFLorenz / Benner / Sorensen - Martinos MGH + HSTGlobal Ipsi Global Contral LocalFollow-upEstimation of CBF vs. AIFsLorenz / Benner / Sorensen - Martinos MGH + HSTProblems (and Potential Solutions)•Monitoring Treatment? •Closing the gap between imaging and clinical outcome–Location matters! •MTT as currently calculated may be overestimating due to delay–Choice of AIF? (delay, dispersion)–New CBF approaches: Local AIF, circular deconvolution•Other markers besides perfusion–Microvascular status–Vasomotion•Imaging Time: still too much time in the scannerMRI Measure of VasomotionShot-to-shot variability of SI in MRI time series due to noise:Shot-to-shot variability of SI in MRI time series due to noise:Non-physiological (e.g., thermal, scanner)Non-physiological (e.g., thermal, scanner)Physiological (e.g., cardiac, respiratory, vasomotion)Physiological (e.g., cardiac, respiratory, vasomotion)Time (Image #)SIHzFTWang / Martinos - MGH -HSTTime (Image #)SIMRI Measure of VasomotionNoise quantified via Noise quantified via standard deviation (SD) or standard deviation (SD) or variance mapsvariance mapsSD MapNo spatial distribution for non-physiological noiseRegional differences in SD reflect physiological noiseRescaledCSF: cardiac, respirationParenchyma: vasomotionMethodsSubjects: 32 acute stroke patientsSubjects: 32 acute stroke patientsMRI (1.5 T):MRI (1.5 T):• Acute Perfusion: <12 h, TR=1.5s, 1.7 mm resolution• Acute Perfusion: <12 h, TR=1.5s, 1.7 mm resolution • • Follow-up T2: >5 dFollow-up T2: >5 dCBF and CBV maps calculated from PWICBF and CBV maps calculated from PWIPre-bolus PWI (~15 images) used to calculate SD mapsPre-bolus PWI (~15 images) used to calculate SD mapspre-bolusWang / Martinos - MGH -HSTSD Differences in Normal TissueSD-PWI differences seen in normal tissue regions SD-PWI differences seen in normal tissue regions Normal white SD < normal gray SD (31 of 32 patients)Normal white SD <