Regional myocardial work by strain Doppler echocardiography and LV pressure: a new method for quantifying myocardial function

There is a need for better methods to quantify regional myocardial function. In the present study, we investigated the feasibility of quantifying regional function in terms of a segmental myocardial work index as derived from strain Doppler echocardiography (SDE) and invasive pressure. In 10 anesthetized dogs, we measured left ventricular (LV) pressure by micromanometer and myocardial longitudinal strains by SDE and sonomicrometry. The regional myocardial work index (RMWI) was calculated as the area of the pressure-strain loop. As a reference method for strain, we used sonomicrometry. By convention, the loop area was assigned a positive sign when the pressure-strain coordinates rotated counterclockwise. Measurements were done at baseline and during volume loading and left anterior descending coronary artery (LAD) occlusion, respectively. There was a good correlation between RMWI calculated from strain by SDE and strain by sonomicrometry (y = 0.73x + 0.21, r = 0.82, P < 0.01). Volume loading caused an increase in RMWI from 1.3 +/- 0.2 to 2.2 +/- 0.1 kJ/m3 (P < 0.05) by SDE and from 1.5 +/- 0.3 to 2.7 +/- 0.3 kJ/m3 (P = 0.066) by sonomicrometry. Short-term ischemia (1 min) caused a decrease in RMWI from 1.3 +/- 0.2 to 0.3 +/- 0.04 kJ/m3 (P < 0.05) and from 1.3 +/- 0.3 to 0.5 +/- 0.2 kJ/m3 (P < 0.05) by SDE and sonomicrometry, respectively. In the nonischemic ventricle and during short-term ischemia, the pressure-strain loops rotated counterclockwise, consistent with actively contracting segments. Long-term ischemia (3 h), however, caused the pressure-strain loop to rotate clockwise, consistent with entirely passive segments, and the loop areas became negative, -0.2 +/- 0.1 and -0.1 +/- 0.03 kJ/m3 (P < 0.05) by SDE and sonomicrometry, respectively. A RMWI can be estimated by SDE in combination with LV pressure. Furthermore, the orientation of the loop can be used to assess whether the segment is active or passive.     

Load-independent index of diastolic filling: model-based derivation with in vivo validation in control and diastolic dysfunction subjects.

Maximum elastance is an experimentally validated, load-independent systolic function index stemming from the time-varying elastance paradigm that decoupled extrinsic load from (intrinsic) contractility. Although Doppler echocardiography is the preferred method of diastolic function (DF) assessment, all echo-derived indexes are load dependent, and no invasive or noninvasive load-independent index of filling (LIIF) exists. In this study, we derived and experimentally validated a LIIF. We used a kinematic filling paradigm (the parameterized diastolic filling formalism) to predict and derive the (dimensionless) dynamic diastolic efficiency M, defined by the slope of the peak driving force [maximum driving force (kx(o)) proportional, variant peak atrioventricular (AV) gradient] to maximum viscoelastic resistive force [peak resistive force (cE(peak))] relation. To validate load independence, we analyzed E-waves recorded while load was varied via tilt table (head up, horizontal, and head down) in 16 healthy volunteers. For the group, linear regression of E-wave derived kx(o) vs. cE(peak) yielded kx(o) = M (cE(peak)) + B, r2 = 0.98; where M = 1.27 +/- 0.09 and B = 5.69 +/- 1.70. Effects of diastolic dysfunction (DD) on M were assessed by analysis of preexisting simultaneous cath-echo data in six DD vs. five control subjects. Average M for the DD group (M = 0.98 +/- 0.07) was significantly lower than controls (M = 1.17 +/- 0.05, P < 0.001). We conclude that M is a LIIF because it uncouples intrinsic DF (i.e., the pressure-flow relation) from extrinsic load (left ventricular end-diastolic pressure). Larger M values imply better DF in that increasing AV pressure gradient results in relatively smaller increases in peak resistive losses (cE(peak)). Conversely, lower M implies that increasing AV gradient leads to larger increases in resistive losses. Further prospective validation characterizing M in well-defined pathological states is warranted.     

Contribution of mitral annular dynamics to LV diastolic filling with alteration in preload and inotropic state

Mitral annular (MA) excursion during diastole encompasses a volume that is part of total left ventricular (LV) filling volume (LVFV). Altered excursion or area variation of the MA due to changes in preload or inotropic state could affect LV filling. We hypothesized that changes in LV preload and inotropic state would not alter the contribution of MA dynamics to LVFV. Six sheep underwent marker implantation in the LV wall and around the MA. After 7-10 days, biplane fluoroscopy was used to obtain three-dimensional marker dynamics from sedated, closed-chest animals during control conditions, inotropic augmentation with calcium (Ca), preload reduction with nitroprusside (N), and vena caval occlusion (VCO). The contribution of MA dynamics to total LVFV was assessed using volume estimates based on multiple tetrahedra defined by the three-dimensional marker positions. Neither the absolute nor the relative contribution of MA dynamics to LVFV changed with Ca or N, although MA area decreased (Ca, P < 0.01; and N, P < 0.05) and excursion increased (Ca, P < 0.01). During VCO, the absolute contribution of MA dynamics to LVFV decreased (P < 0.001), based on a reduction in both area (P < 0.001) and excursion (P < 0.01), but the relative contribution to LVFV increased from 18 +/- 4 to 45 +/- 13% (P < 0.001). Thus MA dynamics contribute substantially to LV diastolic filling. Although MA excursion and mean area change with moderate preload reduction and inotropic augmentation, the contribution of MA dynamics to total LVFV is constant with sizeable magnitude. With marked preload reduction (VCO), the contribution of MA dynamics to LVFV becomes even more important.     

Time-varying effective mitral valve area: prediction and validation using cardiac MRI and Doppler echocardiography in normal subjects

Precise knowledge of the volume and rate of early rapid left ventricular (LV) filling elucidates kinematic aspects of diastolic physiology. The Doppler E wave velocity-time integral (VTI) is conventionally used as the estimate of early, rapid-filling volume; however, this implicitly requires the assumption of a constant effective mitral valve area (EMVA). We sought to evaluate whether the EMVA is truly constant throughout early, rapid filling in 10 normal subjects using cardiac magnetic resonance imaging (MRI) and contemporaneous Doppler echocardiography, which were synchronized via ECG. LV volume measurements as a function of time were obtained via MRI, and transmitral flow values were measured via Doppler echocardiography. The synchronized data were used to predict EMVA as a function of time during early diastole. Validation involved EMVA determination using 1) the short-axis echocardiographic images near the mitral valve leaflet tips, 2) the distance between leaflet tips in the echocardiographic parasternal long-axis view, and 3) the distance between leaflet tips from the MRI LV outflow tract view. Predicted EMVA values varied substantially during early rapid filling, and observed EMVA values agreed well with predictions. We conclude that the EMVA is not constant, and its variation causes LV volume to increase faster than is reflected by the VTI. These results reveal the mechanism of early rapid volumetric increase and directly affect the significance and physiological interpretation of the VTI of the Doppler E wave. Application to subjects in selected pathophysiological subsets is in progress.     

Assessment of central venous catheterization in a simulated model using a motion-tracking device: an experimental validation study

Background

Central venous catheterization (CVC) is a basic requirement for many medical specialties. Simulated training in CVC may allow the acquisition of this competency but few reports have established a valid methodology for learning and acquiring procedural skills for CVC. This study aims to validate the use of a tracking motion device, the imperial college surgical assessment device (ICSAD), by comparing it with validated global rating scales (GRS) to measure CVC performance in a simulated torso.

Methods

Senior year medical students, first and last year residents (PGY1, LYR), and expert anesthesiologists performed a jugular CVC assessment in a simulated model (Laerdal IV Torso). A validated GRS for objective assessment of technical skills and motion analysis by ICSAD was used. Statistical analysis was performed through Mann–Whitney and Kruskal–Wallis tests for construct validity and Spearman correlation coefficients between the ICSAD and GRS scores for concurrent validity between both.

Results

32 subjects were recruited (10 medical students, 8 PGY1, 8 LYR and 8 experts). Total path length measured with ICSAD and GRS scores were significantly different between all groups, except for LYR compared to experts (p = 0.664 for GRS and p = 0.72 for ICSAD). Regarding jugular CVC procedural time, LYR and experts were faster than PGY1 and MS (p < 0.05). Spearman correlation coefficient was ?0.684 (p < 0.001) between ICSAD and GRS scores.

Conclusions

ICSAD is a valid tool for assessment of jugular CVC since it differentiates between expert and novice subjects, and correlates with a validated GRS for jugular CVC in a simulated torso.

     

A new automated method for the quantification of mitral regurgitant volume and dynamic regurgitant orifice area based on a normalized centerline velocity distribution using color M-mode and continuous wave Doppler imaging

Previous echocardiographic techniques for quantifying valvular regurgitation (PISA) are limited by factors including uncertainties in orifice location and hemispheric convergence assumption. Using computational fluid dynamics simulations, we developed a new model for the estimation of orifice diameter and regurgitant volume without the aforementioned assumptions of the PISA technique. Using experimental data obtained from the in vitro flow model we successfully validated our new model. The model output (y) and reference (x) values were in close agreement (y = 0.95x + 0.38, r = 0.96, error = 1.68 +/- 7.54% for the orifice diameter and y = 1.18x - 4.72, r = 0.93, error = 6.48 +/- 16.81% for the regurgitant volume).     

Assessment of LV ejection fraction using real-time 3D echocardiography in daily practice: direct comparison of the volumetric and speckle tracking methodologies to CMR

Aims

This study is the first to directly compare two widely used real-time 3D echocardiography (RT3DE) methods of cardiac magnetic resonance imaging (CMR) and assess their reproducibility in experienced and less experienced observers.

Methods

Consecutive patients planned for CMR underwent RT3DE within 8 h of CMR with Philips (volumetric method) and Toshiba Artida (speckle tracking method). Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were measured using RT3DE, by four trained observers, and compared with CMR values.

Results

Thirty-five patients were included (49.7 ± 15.7 years; 55 % male), 30 (85.7 %) volumetric and 27 (77.1 %) speckle tracking datasets could be analysed. CMR derived LVEDV, LVESV and LVEF were 198 ± 58 ml, 106 ± 53 ml and 49 ± 15 %, respectively. LVEF derived from speckle tracking was accurate and reproducible in all observers (all intra-class correlation coefficients (ICC) > 0.86). LVEF derived from the volumetric method correlated well to CMR in experienced observers (ICC 0.85 and 0.86) but only moderately in less experienced observers (ICC 0.58 and 0.77) and was less reproducible in these observers (ICC = 0.55). Volumes were significantly underestimated compared with CMR (p < 0.001).

Conclusion

This study demonstrates that both RT3DE methodologies are sufficiently accurate and reproducible for use in daily practice. However, experience importantly influences the accuracy and reproducibility of the volumetric method, which should be considered when introducing this technique into clinical practice.     

Intraoperative two-dimensional echocardiography and color flow Doppler imaging: a basic transesophageal single plane patient examination sequence.

Recent advances in technology have allowed application of transesophageal echocardiography to intraoperative care of critically ill patients. Early clinical application primarily involved evaluation of left ventricular regional wall motion. However, valid intraoperative use of transesophageal echocardiography should also encompass systematic assessment of the entire heart as well as the great vessels. This report describes a 10-step sequence of single plane, two-dimensional echocardiographic views which constitute a basic patient examination capable of being performed by a practitioner whose primary responsibility is the delivery of anesthesia care. A 5-step color flow Doppler examination sequence is also presented. These views complement the two-dimensional echocardiographic steps. Representations of methods for grading Doppler-defined valvular regurgitation complete the report.     

Assessment of left ventricular diastolic suction in dogs using wave-intensity analysis

Two apparently different types of mechanisms have emerged to explain diastolic suction (DS), that property of the left ventricle (LV) that tends to cause it to refill itself during early diastole independent of any force from the left atrium (LA). By means of the first mechanism, DS depends on decreased elastance [e.g., the relaxation time constant (tau)] and, by the second, end-systolic volume (V(LVES)). We used wave-intensity analysis (WIA) to measure the total energy transported by the backward expansion wave (I(W-)) during LV relaxation in an attempt to reconcile these mechanisms. In six anesthetized, open-chest dogs, we measured aortic, LV (P(LV)), LA (P(LA)), and pericardial pressures and LV volume by orthogonal ultrasonic crystals. Mitral velocity was measured by Doppler echocardiography, and aortic velocity was measured by an ultrasonic flow probe. Heart rate was controlled by pacing, V(LVES) by volume loading, and tau by isoproterenol or esmolol administration. I(W-) was found to be inversely related to tau and V(LVES). Our measure of DS, the energy remaining after mitral valve opening, I(W-DS), was also found to be inversely related to tau and V(LVES) and was approximately 10% of the total "aspirating" energy generated by LV relaxation (i.e., I(W-)). The size of the Doppler (early filling) E wave depended on I(W-DS) in addition to I(W+), the energy associated with LA decompression. We conclude that the energy of the backward-going wave generated by the LV during relaxation depends on both the rate at which elastance decreases (i.e., tau) and V(LVES). WIA provides a new approach for assessing DS and reconciles those two previously proposed mechanisms. The E wave depends on DS in addition to LA decompression.     

Cryopreservation of skin using a murine model: validation of a prognostic viability assay

In order to evaluate the many variables that can affect cryopreservation success, a simple, highly reproducible model system is required. We have evaluated the use of tetrazolium reductase activity as a prognostic indicator of skin viability in an inbred murine model. Two inbred hairless mouse strains were characterized in studies on autografting and allografting following different skin-storage protocols. Skin tetrazolium reductase (TR) activity correlated well with oxygen consumption, and with graft success--the ultimate performance criterion--following varying degrees of cryogenic injury. The assay was shown to be highly reproducible. In a series of factorial experiments the only factors affecting TR activity were those concerning the mouse donors, i.e., mouse strain, age, sex, and body area. The effects of these factors on TR activity were fully characterized.     

Assessment of left ventricular systolic and diastolic abnormalities in patients with hypertrophic cardiomyopathy using real-time three-dimensional echocardiography and two-dimensional speckle tracking imaging

Background

Conventional echocardiography is not sensitive enough to assess left ventricular (LV) dysfunction in hypertrophic cardiomyopathy (HCM) patients. This research attempts to find a new ultrasonic technology to better assess LV diastolic function, systolic function, and myocardial longitudinal and circumferential systolic strain of segments with different thicknesses in HCM patients.

Methods

This study included 50 patients with HCM and 40 healthy subjects as controls. The peak early and late mitral annulus diastolic velocities at six loci (E_a′ and A_a′, respectively) and the E_a′/A_a′ ratio were measured using real-time tri-plane echocardiography and quantitative tissue velocity imaging (RT-3PE-QTVI). The mean value of E_a′ at six loci (E_m′) was obtained for the calculation of E/E_m′ ratio. The LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), and LV ejection fraction (LVEF) were measured using real-time three-dimensional echocardiography (RT-3DE). LV myocardial longitudinal peak systolic strain (LPSS) and circumferential peak systolic strain (CPSS) in the apical-middle-basal segments (LPSS_-api, LPSS_-mid, LPSS_-bas; CPSS_-api, CPSS_-mid, and CPSS_-bas, respectively) were obtained using a software for two-dimensional speckle tracking imaging (2D-STI). According to the different segmental thicknesses (STs) in each HCM patient, the values (LPSS and CPSS) of all the myocardial segments were categorized into three groups and the respective averages were computed.

Results

The E_a′, A_a′, and, E_a′/A_a’ ratio in HCM patients were lower than those in the controls (all p?<?0.001), while the E/E_m′ ratio in HCM patients was higher than that in the controls (p?<?0.001). The LVEDV, LVSV, and LVEF were significantly lower in HCM patients than in controls (all p?<?0.001). In HCM patients, the LPSS_-api, LPSS_-mid, LPSS_-bas, CPSS_-api, CPSS_-mid, and CPSS_-bas and the LPSS and CPSS of LV segments with different thicknesses were all significantly reduced (all p?<?0.001).

Conclusions

In HCM patients, myocardial dysfunction was widespread not only in the obviously hypertrophic segments but also in the non-hypertrophic segments; the LV systolic and diastolic functions were damaged, even with a normal LVEF. LV diastolic dysfunction, systolic dysfunction, and myocardial deformation impairment in HCM patients can be sensitively revealed by RT-3PE-QTVI, RT-3DE, and 2D-STI.

     

Chronic inhibition of fatty acid oxidation: new model of diastolic dysfunction

The proportion of cardiac energy derived from fatty acid oxidation decreases and that derived from glucose increases during ischemia. This biochemical profile of cardiac energy production is achieved in rats and mice without ischemia by pharmacological agents such as tetradecylglycidic acid. Chronically this leads to increased cardiac stiffness, and hypertrophy in the rodent models. Elements of human cardiac dysfunction are hypothesized to develop from and/or cause similar changes in substrate utilization for energy production. For some individuals treatment that would prevent or reverse these changes may be appropriate.     

Validation of a mouse conductance system to determine LV volume: comparison to echocardiography and crystals

The application of left ventricular pressure-volume analysis to transgenic mice to characterize the cardiac phenotype has been problematic due to the small size of the mouse heart and the rapid heartbeat. Conductance technology has been miniaturized for the mouse and can solve this problem. However, there has been no validation of this technique. Accordingly, we performed echocardiography followed by simultaneous ultrasonic crystals, flow probe, and conductance studies in 18 CD-1 mice. Raw conductance volumes were corrected for an inhomogenous electrical field (alpha) and parallel conductance (G(pi)) yielding a stroke volume of 14.1 +/- 3.7 microliter/beat, end-diastolic volume of 20.8 +/- 6.5 microliter, and end-systolic volume of 9.0 +/- 5.8 microliter. The mean conductance volumes were no different from those derived by flow probe and echocardiography but did differ from ultrasonic crystals. G(pi) was determined to be 14.9 +/- 8.7 microliter. However, hypertonic saline altered dimension and pressure in the mouse left ventricle. Although G(pi) can be determined by the hypertonic saline method, saline altered hemodynamics, questioning its validity in the mouse. Although mean measures of absolute volume may be similar among different techniques, individual values did not correlate.     

Characterisation and validation of a new murine model of global ischaemia-reperfusion injury

A specially designed Langendorff apparatus was constructed to allow perfusion of the isolated mouse heart. Hearts were randomised into groups to receive differing periods of global (zero flow) ischaemia or continuous perfusion (controls). During reperfusion, recovery of baseline force was recorded and perfusate collected for LDH assay (U/L/g wet weight). After 30 min reperfusion, hearts were stained with tetrazolium and planimetry performed to measure infarct size. Dose-response relationships were demonstrated for all 3 end-points against duration of ischaemic insult. Functional recovery and enzyme leakage correlated well with infarct size (r = 0.77, p < 0.001 and r = 0.73, p < 0.001 respectively). Transgenic mice may now be used to study the effect of specific phenotypic changes on the pathogenesis of ischaemia-reperfusion injury using a reliable and reproducible technique.     

Direct visualization of blood flow through the interaortic foramen of the eastern diamondback rattlesnake, Crotalus adamanteus, using echocardiography and color Doppler imaging

The bases of the left and right aortae in snakes are joined by the interaortic foramen. Previous anatomical and physiological studies have raised the possibility of blood flow through this foramen playing an important role in the redistribution of blood throughout the body, particularly during periods of hemostatic stress. Echocardiography was employed to view the heart of unanesthetized specimens of the eastern diamondback rattlesnake, Crotalus adamanteus. The echocardiographic images, and particularly the color Doppler imaging, revealed that the patency of the interaortic foramen changes during the cardiac cycle, and that blood regularly flowed through the interaortic foramen between the two aortae. J. Exp. Zool. 284:742-745, 1999. Copyright 1999 Wiley-Liss, Inc.     

Simulation of planar soft tissues using a structural constitutive model: Finite element implementation and validation

Computational implementation of physical and physiologically realistic constitutive models is critical for numerical simulation of soft biological tissues in a variety of biomedical applications. It is well established that the highly nonlinear and anisotropic mechanical behaviors of soft tissues are an emergent behavior of the underlying tissue microstructure. In the present study, we have implemented a structural constitutive model into a finite element framework specialized for membrane tissues. We noted that starting with a single element subjected to uniaxial tension, the non-fibrous tissue matrix must be present to prevent unrealistic tissue deformations. Flexural simulations were used to set the non-fibrous matrix modulus because fibers have little effects on tissue deformation under three-point bending. Multiple deformation modes were simulated, including strip biaxial, planar biaxial with two attachment methods, and membrane inflation. Detailed comparisons with experimental data were undertaken to insure faithful simulations of both the macro-level stress–strain insights into adaptations of the fiber architecture under stress, such as fiber reorientation and fiber recruitment. Results indicated a high degree of fidelity and demonstrated interesting microstructural adaptions to stress and the important role of the underlying tissue matrix. Moreover, we apparently resolve a discrepancy in our 1997 study (Billiar and Sacks, 1997. J. Biomech. 30 (7), 753–756) where we observed that under strip biaxial stretch the simulated fiber splay responses were not in good agreement with the experimental results, suggesting non-affine deformations may have occurred. However, by correctly accounting for the isotropic phase of the measured fiber splay, good agreement was obtained. While not the final word, these simulations suggest that affine fiber kinematics for planar collagenous tissues is a reasonable assumption at the macro level. Simulation tools such as these are imperative in the design and simulation of native and engineered tissues.     

Evolution of avian plumage color in a tetrahedral color space: a phylogenetic analysis of new world buntings

We use a tetrahedral color space to describe and analyze male plumage color variation and evolution in a clade of New World buntings--Cyanocompsa and Passerina (Aves: Cardinalidae). The Goldsmith color space models the relative stimulation of the four retinal cones, using the integrals of the product of plumage reflectance spectra and cone sensitivity functions. A color is represented as a vector defined by the relative stimulation of the four cone types--ultraviolet, blue, green, and red. Color vectors are plotted in a tetrahedral, or quaternary, plot with the achromatic point at the origin and the ultraviolet/violet channel along the Z-axis. Each color vector is specified by the spherical coordinates theta, phi, and r. Hue is given by the angles theta and phi. Chroma is given by the magnitude of r, the distance from the achromatic origin. Color vectors of all distinct patches in a plumage characterize the plumage color phenotype. We describe the variation in color space occupancy of male bunting plumages, using various measures of color contrast, hue contrast and diversity, and chroma. Comparative phylogenetic analyses using linear parsimony (in MacClade) and generalized least squares (GLS) models (in CONTINUOUS) with a molecular phylogeny of the group document that plumage color evolution in the clade has been very dynamic. The single best-fit GLS evolutionary model of plumage color variation over the entire clade is a directional change model with no phylogenetic correlation among species. However, phylogenetic innovations in feather color production mechanisms--derived pheomelanin and carotenoid expression in two lineages--created new opportunities to colonize novel areas of color space and fostered the explosive differentiation in plumage color. Comparison of the tetrahedral color space of Goldsmith with that of Endler and Mielke demonstrates that both provide essentially identical results. Evolution of avian ultraviolet/violet opsin sensitivity in relation to chromatic experience is discussed.     

Assessment of segmental wall motion abnormalities using contrast two-dimensional echocardiography in awake mice

Murine models of cardiac disease are becoming an important tool for studying pathophysiological processes. Development of methods to accurately assess ventricular function are therefore important. The purpose of this study was to evaluate the feasibility of echocardiographic assessment of segmental wall motion abnormalities in a murine model of myocardial infarction. Two-dimensional contrast (C+) and noncontrast (C-) echocardiography were performed in 76 awake mice 2 days before and 2 days after left coronary ligation. The short-axis images obtained with two-dimensional echocardiography and corresponding postmortem cross-sectional histological samples stained with Evans blue dye were each divided into 16 segments, and all matched segments were examined for correlation between wall motion abnormalities and myocardial hypoperfusion. With the use of contrast enhancement, the number of visualized segments was significantly increased (base: C- 86%, C+ 98%; midpapillary: C- 57%, C+ 89%; apex: C- 30%, C+ 74%). Agreement between echocardiographically assessed regional wall motion abnormalities and pathologically determined hypoperfusion in basal, midpapillary, and apical levels were 90%, 93%, and 93%, respectively. Agreement between echocardiographically normal wall motion and pathologically normal findings in basal, midpapillary, and apical levels were 99%, 88%, and 71%, respectively. Thus echocardiographic assessment of segmental wall motion in awake mice was feasible and the accuracy was improved with the use of a contrast agent.     

Brightness contrast inhibits color induction: evidence for a new kind of color theory

A gray region can be made to look colored by a colored surround. This phenomenon, chromatic induction, depends on color differences around the boundary of the region. We performed experiments on chromatic induction with small, initially achromatic, targets on nine different colored surrounds ranging in color from blue to red. Using scaling of saturation as our measure of perceived color strength, we found that chromatic induction is at its maximum when the brightness contrast at the boundary between target and surroundings is minimal. This implies that the neural mechanism in the cerebral cortex that mediates the appearance of brightness at a boundary inhibits the activity of chromatic mechanisms at that same boundary. Observers matched the apparent brightness and luminance of each of the colored surrounds. For surround colors where brightness and luminance matches differ, brightness contrast, not luminance contrast, controls chromatic induction. These new findings, taken together with other evidence, require a new theory of color appearance that includes mutually inhibitory interactions between color and brightness mechanisms that are sensing color and brightness contrast at visual boundaries.