The bolus arrival time (BAT) based on an indicator dilution curve is an important hemodynamic parameter. As the direct estimation of this parameter is generally problematic, various parametric models have been proposed that describe typical physiological shapes of indicator dilution curves, but it remains unclear which model describes the real physiological background. This article presents a method that indirectly incorporates physiological information derived from the data available. For this, a patient-specific hemodynamic reference curve is extracted, and the corresponding reference BAT is determined. To estimate a BAT for a given signal curve, the reference curve is fitted linearly to the signal curve. The parameters of the fitting process are then used to transfer the reference BAT to the signal curve. The validation of the method proposed based on Monte Carlo simulations showed that the approach presented is capable of improving the BAT estimation precision compared with standard BAT estimation methods by up to 59% while at the same time reduces the computation time. A major benefit of the method proposed is that no assumption about the underlying distribution of indicator dilution has to be made, as it is implicitly modeled in the reference curve. Magn Reson Med 65:289-294, 2011. V C 2010 Wiley-Liss, Inc. Key words: magnetic resonance angiography; indicator dilution techniques; hemodynamics; curve fitting; computer simulation Indicator dilution techniques depend on the fact that an indicator substance is injected into a blood vessel upstream and dilutes downstream, where its concentration time curve, often referred to as indicator dilution curve (IDC) (1), can be measured using a variety of techniques. In general, an IDC s(t) represents the density of the applied contrast agent at time point t.The history of indicator dilution methods for blood flow quantification is long. Already in 1824, Hering introduced an indicator dilution method for measuring blood velocity; since then, these methods have been successfully applied in metabolic and circulatory studies (2). Examples for clinical applications of IDCs involve cardiac output quantification (3), detection of brain ischemia (4), analysis of pathological blood flow changes caused by vascular malformations, (5) or characterization of brain tumor vascularization (6).Classically, IDCs were obtained by catheter based acquisition of dye-dilution and thermodilution curves. The development of improved imaging techniques such as digital subtraction angiography and four-dimensional (4D) MRI made it possible to assess the hemodynamic situation of the whole vascular system.The digital subtraction angiography has historically been central for diagnosis and treatment of many central nervous system diseases. However, it is an invasive procedure with potentially severe complications, but the spatial (0.2 mm) and temporal resolution (0.25 sec) remain incomparable. Recent development of 4D MR angiography (MRA) enables an improved rating of cerebral diseases, while reducin...