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At clinical MRI field strengths (1.5 and 3 T), quantitative maps of the longitudinal relaxation time T1 of the myocardium reveal diseased tissue without requiring contrast agents. Cardiac T1 maps can be measured by Look-Locker inversion recovery sequences such as ShMOLLI at 1.5 and 3 T. Cardiovascular MRI at a field strength of 7 T has recently become feasible, but doubts have remained as to whether magnetization inversion is possible in the heart due to subject heating and technical limitations. This work extends the repertoire of 7 T cardiovascular MRI by implementing an adiabatic inversion pulse optimized for use in the heart at 7 T. A "ShMOLLI+IE" adaptation of the ShMOLLI pulse sequence has been introduced together with new postprocessing that accounts for the possibility of incomplete magnetization inversion. These methods were validated in phantoms and then used in a study of six healthy volunteers to determine the degree of magnetization inversion and the T1 of normal myocardium at 7 T within a 22-heartbeat breathhold. Using a scanner with 16 × 1 kW radiofrequency outputs, inversion efficiencies ranging from -0.79 to -0.83 (intrasegment means; perfect 180° would give -1) were attainable across the myocardium. The myocardial T1 was 1925 ± 48 ms (mean ± standard deviation)., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: Quantitative mapping of the native T1 of the heart using the modified look-locker inversion recovery (MOLLI) technique provides high quality diagnostic information without requiring contrast agents. Previous work has considered the effects of T2 relaxation on MOLLI T1 measurements, finding that the T1 measured by MOLLI is biased, and that Saturation-recovery single-Shot Acquisition generates a more precise T1. However, despite detailed experiments and simulation the exact relaxation times observed in vivo remain unexplained, but might be due to magnetization transfer (MT)., Methods: We used an MT simulation based on the Bloch-McConnell equations to evaluate the most common MOLLI and saturation-recovery single-shot acquisition sequence variants., Results: For myocardial tissue we find that the T1 measured by saturation-recovery single-shot acquisition is insensitive to MT and T2, whereas MT reduces the T1 measured by MOLLI (>10%) in addition to the effects due to T2 relaxation., Conclusions: The consequences of this T1 underestimation by MOLLI are relevant. Increases in the actual T1 and T2 and decreases in MT will all result in an increase in T1 measured by MOLLI. Myocardial infarction demonstrates increased native T1 and T2 and decreased MT, indicating that these biases enhance the sensitivity of MOLLI to detect this and possibly other cardiovascular disease states., (Copyright © 2013 Wiley Periodicals, Inc.)

Objectives: This study sought to explore the potential role of noncontrast myocardial T1 mapping for detection of cardiac involvement in patients with primary amyloid light-chain (AL) amyloidosis., Background: Cardiac involvement carries a poor prognosis in systemic AL amyloidosis. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is useful for the detection of cardiac amyloid, but characteristic LGE patterns do not always occur or they appear late in the disease. Noncontrast characterization of amyloidotic myocardium with T1 mapping may improve disease detection. Furthermore, quantitative assessment of myocardial amyloid load would be of great value., Methods: Fifty-three AL amyloidosis patients (14 with no cardiac involvement, 11 with possible involvement, and 28 with definite cardiac involvement based on standard biomarker and echocardiographic criteria) underwent CMR (1.5-T) including noncontrast T1 mapping (shortened modified look-locker inversion recovery [ShMOLLI] sequence) and LGE imaging. These were compared with 36 healthy volunteers and 17 patients with aortic stenosis and a comparable degree of left ventricular hypertrophy as the cardiac amyloid patients., Results: Myocardial T1 was significantly elevated in cardiac AL amyloidosis patients (1,140 ± 61 ms) compared to normal subjects (958 ± 20 ms, p < 0.001) and patients with aortic stenosis (979 ± 51 ms, p < 0.001). Myocardial T1 was increased in AL amyloid even when cardiac involvement was uncertain (1,048 ± 48 ms) or thought absent (1,009 ± 31 ms). A noncontrast myocardial T1 cutoff of 1,020 ms yielded 92% accuracy for identifying amyloid patients with possible or definite cardiac involvement. In the AL amyloidosis cohort, there were significant correlations between myocardial T1 time and indices of systolic and diastolic dysfunction., Conclusions: Noncontrast T1 mapping has high diagnostic accuracy for detecting cardiac AL amyloidosis, correlates well with markers of systolic and diastolic dysfunction, and is potentially more sensitive for detecting early disease than LGE imaging. Elevated myocardial T1 may represent a direct marker of cardiac amyloid load. Further studies are needed to assess the prognostic significance of T1 elevation., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Quantitative T1-mapping is rapidly becoming a clinical tool in cardiovascular magnetic resonance (CMR) to objectively distinguish normal from diseased myocardium. The usefulness of any quantitative technique to identify disease lies in its ability to detect significant differences from an established range of normal values. We aimed to assess the variability of myocardial T1 relaxation times in the normal human population estimated with recently proposed Shortened Modified Look-Locker Inversion recovery (ShMOLLI) T1 mapping technique., Methods: A large cohort of healthy volunteers (n = 342, 50% females, age 11-69 years) from 3 clinical centres across two countries underwent CMR at 1.5T. Each examination provided a single average myocardial ShMOLLI T1 estimate using manually drawn myocardial contours on typically 3 short axis slices (average 3.4 ± 1.4), taking care not to include any blood pool in the myocardial contours. We established the normal reference range of myocardial and blood T1 values, and assessed the effect of potential confounding factors, including artefacts, partial volume, repeated measurements, age, gender, body size, hematocrit and heart rate., Results: Native myocardial ShMOLLI T1 was 962 ± 25 ms. We identify the partial volume as primary source of potential error in the analysis of respective T1 maps and use 1 pixel erosion to represent "midwall myocardial" T1, resulting in a 0.9% decrease to 953 ± 23 ms. Midwall myocardial ShMOLLI T1 was reproducible with an intra-individual, intra- and inter-scanner variability of ≤2%. The principle biological parameter influencing myocardial ShMOLLI T1 was the female gender, with female T1 longer by 24 ms up to the age of 45 years, after which there was no significant difference from males. After correction for age and gender dependencies, heart rate was the only other physiologic factor with a small effect on myocardial ShMOLLI T1 (6ms/10bpm). Left and right ventricular blood ShMOLLI T1 correlated strongly with each other and also with myocardial T1 with the slope of 0.1 that is justifiable by the resting partition of blood volume in myocardial tissue. Overall, the effect of all variables on myocardial ShMOLLI T1 was within 2% of relative changes from the average., Conclusion: Native T1-mapping using ShMOLLI generates reproducible and consistent results in normal individuals within 2% of relative changes from the average, well below the effects of most acute forms of myocardial disease. The main potential confounder is the partial volume effect arising from over-inclusion of neighbouring tissue at the manual stages of image analysis. In the study of cardiac conditions such as diffuse fibrosis or small focal changes, the use of "myocardial midwall" T1, age and gender matching, and compensation for heart rate differences may all help to improve the method sensitivity in detecting subtle changes. As the accuracy of current T1 measurement methods remains to be established, this study does not claim to report an accurate measure of T1, but that ShMOLLI is a stable and reproducible method for T1-mapping.

Background: Myocardial extracellular volume (ECV) is elevated in fibrosis or infiltration and can be quantified by measuring the haematocrit with pre and post contrast T1 at sufficient contrast equilibrium. Equilibrium CMR (EQ-CMR), using a bolus-infusion protocol, has been shown to provide robust measurements of ECV using a multibreath-hold T1 pulse sequence. Newer, faster sequences for T1 mapping promise whole heart coverage and improved clinical utility, but have not been validated., Methods: Multibreathhold T1 quantification with heart rate correction and single breath-hold T1 mapping using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) were used in equilibrium contrast CMR to generate ECV values and compared in 3 ways.Firstly, both techniques were compared in a spectrum of disease with variable ECV expansion (n=100, 50 healthy volunteers, 12 patients with hypertrophic cardiomyopathy, 18 with severe aortic stenosis, 20 with amyloid). Secondly, both techniques were correlated to human histological collagen volume fraction (CVF%, n=18, severe aortic stenosis biopsies). Thirdly, an assessment of test:retest reproducibility of the 2 CMR techniques was performed 1 week apart in individuals with widely different ECVs (n=10 healthy volunteers, n=7 amyloid patients)., Results: More patients were able to perform ShMOLLI than the multibreath-hold technique (6% unable to breath-hold). ECV calculated by multibreath-hold T1 and ShMOLLI showed strong correlation (r(2)=0.892), little bias (bias -2.2%, 95%CI -8.9% to 4.6%) and good agreement (ICC 0.922, range 0.802 to 0.961, p<0.0001). ECV correlated with histological CVF% by multibreath-hold ECV (r(2)= 0.589) but better by ShMOLLI ECV (r(2)= 0.685). Inter-study reproducibility demonstrated that ShMOLLI ECV trended towards greater reproducibility than the multibreath-hold ECV, although this did not reach statistical significance (95%CI -4.9% to 5.4% versus 95%CI -6.4% to 7.3% respectively, p=0.21)., Conclusions: ECV quantification by single breath-hold ShMOLLI T1 mapping can measure ECV by EQ-CMR across the spectrum of interstitial expansion. It is procedurally better tolerated, slightly more reproducible and better correlates with histology compared to the older multibreath-hold FLASH techniques.

Background: Noncontrast magnetic resonance T1 mapping reflects a composite of both intra- and extracellular signal. We hypothesized that noncontrast T1 mapping can characterize the myocardium beyond that achieved by the well-established late gadolinium enhancement (LGE) technique (which detects focal fibrosis) in both hypertrophic (HCM) and dilated (DCM) cardiomyopathy, by detecting both diffuse and focal fibrosis., Methods and Results: Subjects underwent Cardiovascular Magnetic Resonance imaging at 3T (28 HCM, 18 DCM, and 12 normals). Matching short-axis slices were acquired for cine, T1 mapping, and LGE imaging (0.1 mmol/kg). Circumferential strain was measured in the midventricular slice, and (31)P magnetic resonance spectroscopy was acquired for the septum of the midventricular slice. Mean T1 relaxation time was increased in HCM and DCM (HCM 1209±28 ms, DCM 1225±42 ms, normal 1178±13 ms, P<0.05). There was a weak correlation between mean T1 and LGE (r=0.32, P<0.001). T1 values were higher in segments with LGE than in those without (HCM with LGE 1228±41 ms versus no LGE 1192±79 ms, P<0.01; DCM with LGE 1254±73 ms versus no LGE 1217±52 ms, P<0.01). However, in both HCM and DCM, even in segments unaffected by LGE, T1 values were significantly higher than normal (P<0.01). T1 values correlated with disease severity, being increased as wall thickness increased in HCM; conversely, in DCM, T1 values were highest in the thinnest myocardial segments. T1 values also correlated significantly with circumferential strain (r=0.42, P<0.01). Interestingly, this correlation remained statistically significant even for the slices without LGE (r=0.56, P=0.04). Finally, there was also a statistically significant negative correlation between T1 values and phosphocreatine/adenosine triphosphate ratios (r=-0.59, P<0.0001)., Conclusions: In HCM and DCM, noncontrast T1 mapping detects underlying disease processes beyond those assessed by LGE in relatively low-risk individuals.

Background: T2w-CMR is used widely to assess myocardial edema. Quantitative T1-mapping is also sensitive to changes in free water content. We hypothesized that T1-mapping would have a higher diagnostic performance in detecting acute edema than dark-blood and bright-blood T2w-CMR., Methods: We investigated 21 controls (55 ± 13 years) and 21 patients (61 ± 10 years) with Takotsubo cardiomyopathy or acute regional myocardial edema without infarction. CMR performed within 7 days included cine, T1-mapping using ShMOLLI, dark-blood T2-STIR, bright-blood ACUT2E and LGE imaging. We analyzed wall motion, myocardial T1 values and T2 signal intensity (SI) ratio relative to both skeletal muscle and remote myocardium., Results: All patients had acute cardiac symptoms, increased Troponin I (0.15-36.80 ug/L) and acute wall motion abnormalities but no LGE. T1 was increased in patient segments with abnormal and normal wall motion compared to controls (1113 ± 94 ms, 1029 ± 59 ms and 944 ± 17 ms, respectively; p < 0.001). T2 SI ratio using STIR and ACUT2E was also increased in patient segments with abnormal and normal wall motion compared to controls (all p < 0.02). Receiver operator characteristics analysis showed that T1-mapping had a significantly larger area-under-the-curve (AUC = 0.94) compared to T2-weighted methods, whether the reference ROI was skeletal muscle or remote myocardium (AUC = 0.58-0.89; p < 0.03). A T1 value of greater than 990 ms most optimally differentiated segments affected by edema from normal segments at 1.5 T, with a sensitivity and specificity of 92 %., Conclusions: Non-contrast T1-mapping using ShMOLLI is a novel method for objectively detecting myocardial edema with a high diagnostic performance. T1-mapping may serve as a complementary technique to T2-weighted imaging for assessing myocardial edema in ischemic and non-ischemic heart disease, such as quantifying area-at-risk and diagnosing myocarditis.

Background: Current cardiovascular magnetic resonance (CMR) methods, such as late gadolinium enhancement (LGE) and oedema imaging (T2W) used to depict myocardial ischemia, have limitations. Novel quantitative T1-mapping techniques have the potential to further characterize the components of ischemic injury. In patients with myocardial infarction (MI) we sought to investigate whether state-of the art pre-contrast T1-mapping (1) detects acute myocardial injury, (2) allows for quantification of the severity of damage when compared to standard techniques such as LGE and T2W, and (3) has the ability to predict long term functional recovery., Methods: 3T CMR including T2W, T1-mapping and LGE was performed in 41 patients [of these, 78% were ST elevation MI (STEMI)] with acute MI at 12-48 hour after chest pain onset and at 6 months (6M). Patients with STEMI underwent primary PCI prior to CMR. Assessment of acute regional wall motion abnormalities, acute segmental damaged fraction by T2W and LGE and mean segmental T1 values was performed on matching short axis slices. LGE and improvement in regional wall motion at 6M were also obtained., Results: We found that the variability of T1 measurements was significantly lower compared to T2W and that, while the diagnostic performance of acute T1-mapping for detecting myocardial injury was at least as good as that of T2W-CMR in STEMI patients, it was superior to T2W imaging in NSTEMI. There was a significant relationship between the segmental damaged fraction assessed by either by LGE or T2W, and mean segmental T1 values (P < 0.01). The index of salvaged myocardium derived by acute T1-mapping and 6M LGE was not different to the one derived from T2W (P = 0.88). Furthermore, the likelihood of improvement of segmental function at 6M decreased progressively as acute T1 values increased (P < 0.0004)., Conclusions: In acute MI, pre-contrast T1-mapping allows assessment of the extent of myocardial damage. T1-mapping might become an important complementary technique to LGE and T2W for identification of reversible myocardial injury and prediction of functional recovery in acute MI.

Objectives: The lumbar infusion test is an invasive technique for quantifying cerebrospinal dynamics in patients with hydrocephalus. However, some patients have difficulty tolerating the duration of this procedure. Therefore, we investigated the limits of shortening the test by examining the reliability of cerebrospinal fluid (CSF) compensatory parameters as a function of time., Methods: We analysed recordings of the intracranial cerebral pressure (ICP) response to a constant, high-rate infusion of saline (2 ml/min) lasting 5.7-20 (12 ± 10) min in 30 patients with a preliminary diagnosis of hydrocephalus (13 men, aged 37-81 [65 ± 10] years). We performed computerised identification of CSF outflow resistance (R(out)), intracranial compliance parameters: elastance index (E) and reference pressure (P(0)), based on the truncated ICP response (20-100% of the available test length), estimating either all three parameters (3p method) or only R(out) and E (2p method) assuming P(0) as the regression between the ICP and its amplitude., Results: Following considerable variation during the initial rise of ICP, R(out) typically converged within ± 10% of their final values within 10-15 min. Final R(out) values were 4-40 (12 ± 6) mmHg/ml/min, and were method independent (R(2) = 0.97). Compliance parameters (E, typically 0.1-0.5/ml; P(0): - 10 to + 20 mmHg) agreed poorly between methods (R(2) = 0.3-0.7) and varied considerably within the observed infusion periods., Conclusion: The lumbar infusion test may be shortened to 10-15 min using a rapid infusion rate of 2 ml/min that fulfils the primary objective of obtaining reliable estimates of R(out). This may benefit patients who do not tolerate the full procedure.

Background: T1 mapping allows direct in-vivo quantitation of microscopic changes in the myocardium, providing new diagnostic insights into cardiac disease. Existing methods require long breath holds that are demanding for many cardiac patients. In this work we propose and validate a novel, clinically applicable, pulse sequence for myocardial T1-mapping that is compatible with typical limits for end-expiration breath-holding in patients., Materials and Methods: The Shortened MOdified Look-Locker Inversion recovery (ShMOLLI) method uses sequential inversion recovery measurements within a single short breath-hold. Full recovery of the longitudinal magnetisation between sequential inversion pulses is not achieved, but conditional interpretation of samples for reconstruction of T1-maps is used to yield accurate measurements, and this algorithm is implemented directly on the scanner. We performed computer simulations for 100 ms

Changes in cerebral blood flow (f) and vascular volume (v) are of major interest in mapping cerebral activity and metabolism, but the relation between them currently lacks a sufficient theoretical basis. To address this we considered three models: a uniform reactive tube model (M1); an extension of M1 that includes passive arterial inflow and venous volume (M2); and a more anatomically plausible model (M3) consisting of 19 compartments representing the whole range of vascular sizes and respective CO2 reactivities, derived from literature data. We find that M2 cannot be described as the simple scaling of a tube law, but any divergence from a linear approximation is negligible within the narrow physiological range encountered experimentally. In order to represent correctly the empirically observed slope of the overall v-f relationship, the reactive bed should constitute about half of the total vascular volume, thus including a significant fraction of capillaries and/or veins. Model M3 demonstrates systematic variation of the slope of the v-f relationship between 0.16 and 1.0, depending on the vascular compartment under consideration. This is further complicated when other experimental approaches such as flow velocity are used as substitute measurements. The effect is particularly large in microvascular compartments, but when averaged with larger vessels the variations in slope are contained within 0.25 to 0.55 under conditions typical for imaging methods. We conclude that the v-f relationship is not a fixed function but that both the shape and slope depend on the composition of the reactive volume and the experimental methods used.

Background: Similarity in flow pulsatility has been proposed as a basis for semi-automated segmentation of vessel lumens for MR-based flow measurement, but re-examinations of salient aspects of the methodology have not been widely reported., Methods: 12 normal control subjects underwent repeated (3*Baseline+1*5%CO2) phase contrast measurements of CSF flow through the cerebral aqueduct and foramen magnum, and CBF through the 6 large cranial vessels at the level of the 1st vertebra. Average flows were calculated for regions temporally correlated (0.3 < or = Rthreshold < or = 0.95) to user defined seed points and their 3 x 3 neighbours., Results: Arterial CBF averaged 710ml/min, with low variability (+/- 4%/17%, intra-individual/group CV respectively) and was the only flow to respond significantly to 5%/mmHg CO2. Venous outflow was much smaller (298ml/min +/- 10%/ 72%), possibly due to the weak venous pulse and variable venous anatomy. Average CSF flows exceeded the classical 0.4ml/min CSF production rate and were highly variable--aqueduct: 0.6ml/min (+/- 50%/93%), foramen magnum: -2.7ml/min (+/- 158%/226%)., Conclusions: This preliminary analysis identified procedural steps that can improve the accuracy and repeatability of MR flow measurements, but the process remains user-dependent for the weakly pulsatile foramen magnum CSF and venous flows where variability remains a significant confound even to relatively large perturbations such as CO2 administration.

Combined blood oxygenation level-dependent (BOLD) and arterial spin labeling (ASL) functional MRI (fMRI) was performed for simultaneous investigation of neurovascular coupling in the primary visual cortex (PVC), primary motor cortex (PMC), and supplementary motor area (SMA). The hypercapnia-calibrated method was employed to estimate the fractional change in cerebral metabolic rate of oxygen consumption (CMR(O2)) using both a group-average and a per-subject calibration. The group-averaged calibration showed significantly different CMR(O2)-CBF coupling ratios in the three regions (PVC: 0.34 +/- 0.03; PMC: 0.24 +/- 0.03; and SMA: 0.40 +/- 0.02). Part of this difference emerges from the calculated values of the hypercapnic calibration constant M in each region (M(PVC) = 6.6 +/- 3.4, M(PMC) = 4.3 +/- 3.5, and M(SMA) = 7.2 +/- 4.1), while a relatively minor part comes from the spread and shape of the sensorimotor BOLD-CBF responses. The averages of the per-subject calibrated CMR(O2)-CBF slopes were 0.40 +/- 0.04 (PVC), 0.31 +/- 0.03 (PMC), and 0.44 +/- 0.03 (SMA). These results are 10-30% higher than group-calibrated values, and are potentially more useful for quantifying individual differences in focal functional responses. The group-average calibrated motor coupling value is increased to 0.28 +/- 0.03 when stimulus-correlated increases in end-tidal CO(2) are included. Our results support the existence of regional differences in neurovascular coupling, and argue for the importance of achieving optimal accuracy in hypercapnia calibrations to resolve method-dependent variations in published results.

Object: The aim of this study was to assess the asymmetry of autoregulation between the left and right sides of the brain by using bilateral transcranial Doppler ultrasonography in a cohort of patients with head injuries., Methods: Ninety-six patients with head injuries comprised the study population. All significant intracranial mass lesions were promptly removed. The patients were given medications to induce sedation and paralysis, and artificial ventilation. Arterial blood pressure (ABP) and intracranial pressure (ICP) were monitored in an invasive manner. A strategy based on the patient's cerebral perfusion pressure (CPP = ABP - ICP) was applied: CPP was maintained at a level higher than 70 mm Hg and ICP at a level lower than 25 mm Hg. The left and right middle cerebral arteries were insonated daily, and bilateral flow velocities (FVs) were recorded. The correlation coefficient between the CPP and FV, termed Mx, was calculated and time-averaged over each recording period on both sides. An Mx close to 1 signified that slow fluctuations in CPP produced synchronized slow changes in FV, indicating a defective autoregulation. An Mx close to 0 indicated preserved autoregulation. Computerized tomography scans in all patients were reviewed; the side on which the major brain lesion was located was noted and the extent of the midline shift was determined. Outcome was measured 6 months after discharge. The left-right difference in the Mx between the hemispheres was significantly higher in patients who died than in those who survived (0.16 +/- 0.04 compared with 0.08 +/- 0.01; p = 0.04). The left-right difference in the Mx was correlated with a midline shift (r = -0.42; p = 0.03). Autoregulation was worse on the side of the brain where the lesion was located (p < 0.035)., Conclusions: The left-right difference in autoregulation is significantly associated with a fatal outcome. Autoregulation in the brain is worse on the side ipsilateral to the lesion and on the side of expansion in cases in which there is a midline shift.

Objective: The authors evaluated with bilateral transcranial Doppler (TCD) ultrasonography the norm of interhemispheric difference for several cerebrovascular hemodynamic parameters., Methods: Forty-four volunteers (33 male, 11 female; average age = 21 years; range, 20-23 years) were studied. The authors recorded bilateral systolic, diastolic, and mean flow velocity (FV) and noninvasive systolic, diastolic, and mean arterial blood pressure. Calculated indices included Gosling's pulsatility index (GPI), an index of autoregulation (Mx), critical closing pressure (CCP), and a noninvasive estimator of cerebral perfusion pressure (nCPP). All indices were averaged per side and patient. For each parameter, the left-right correlation coefficient (r2) and the 95% confidence limit of the left-right differences were calculated., Results: All TCD-derived indices displayed significant correlations between the left and right sides: r2 = 0.49 for mean FV (FVm), r2 = 0.66 for GPI, r2 = 0.79 for Mx, r2 = 0.93 for CCP, and r2 = 0.94 for nCPP. The 95% confidence intervals for the left-right differences were 20 cm/s for FVm, 0.16 for GPI, 0.18 for Mx, 13 mm Hg for CCP, and 4.6 mm Hg for nCPP., Conclusions: This study gives the reference values for the assessment of left-right symmetry of cerebral hemodynamics using various TCD-derived indices. These reference values should be useful for clinical studies assessing the left-right asymmetry of cerebral hemodynamics on a daily basis.

Objectives: To define optimal cerebral perfusion pressure (CPPOPT) in individual head-injured patients using continuous monitoring of cerebrovascular pressure reactivity. To test the hypothesis that patients with poor outcome were managed at a cerebral perfusion pressure (CPP) differing more from their CPPOPT than were patients with good outcome., Design: Retrospective analysis of prospectively collected data., Setting: Neurosciences critical care unit of a university hospital., Patients: A total of 114 head-injured patients admitted between January 1997 and August 2000 with continuous monitoring of mean arterial blood pressure (MAP) and intracranial pressure (ICP)., Measurements and Main Results: MAP, ICP, and CPP were continuously recorded and a pressure reactivity index (PRx) was calculated online. PRx is the moving correlation coefficient recorded over 4-min periods between averaged values (6-sec periods) of MAP and ICP representing cerebrovascular pressure reactivity. When cerebrovascular reactivity is intact, PRx has negative or zero values, otherwise PRx is positive. Outcome was assessed at 6 months using the Glasgow Outcome Scale. A total of 13,633 hrs of data were recorded. CPPOPT was defined as the CPP where PRx reaches its minimum value when plotted against CPP. Identification of CPPOPT was possible in 68 patients (60%). In 22 patients (27%), CPPOPT was not found because it presumably lay outside the studied range of CPP. Patients' outcome correlated with the difference between CPP and CPPOPT for patients who were managed on average below CPPOPT (r =.53, p <.001) and for patients whose mean CPP was above CPPOPT (r = -.40, p <.05)., Conclusions: CPPOPT could be identified in a majority of patients. Patients with a mean CPP close to CPPOPT were more likely to have a favorable outcome than those whose mean CPP was more different from CPPOPT. We propose use of the criterion of minimal achievable PRx to guide future trials of CPP oriented treatment in head injured patients.