The ability to monitor biological processes in a functional manner is of crucial importance for MRI. Bioresponsive MRI contrast agents together with a bSSFP imaging technique further improve the potential of this methodology to follow biological functions in a rapid manner.A dendrimeric probe (DSCA) was prepared by coupling an amine-reactive smart-contrast-agent (SCA), derived from the monomeric precursor (MSCA) [1], to the generation 4 PAMAM dendrimer. Relaxometric titrations with Ca2+ were performed at 7T NMR for both DSCA and MSCA. Additionally, the influence of anions [2] was investigated by employing a medium which resembles brain extracellular fluid (BEM) at two different temperatures. The diffusion characteristics of DSCA and MSCA were investigated by means of DLS and/or NMR spectroscopy on the respective Eu3+ analogues in the presence and absence of Ca2+. MRI phantom experiments were performed at 7T using a dual frequency volume coil. For dynamic ratiometric monitoring, special features of the bSSFP sequence, such as T2/T1w contrast and highest SNRt of all imaging sequences were exploited [3]. Four tubes containing solutions of SCAs with increasing [Ca2+] were inserted in a 20 mL syringe filled with an aqueous solution of Dotarem®. T­1 and T2 times were determined from respective T1 ­and T2 maps using IR-RARE and MSME sequences. Subsequently, numerical CNR optimization based on Bloch simulations that optimize the signal difference for different contrast agents of acquisition parameters for T1-(FLASH), T2-(RARE) and T2/T1-(bSSFP) weighted imaging was performed for each set of tubes (DSCA or MSCA). Relaxometric titrations revealed an increase in r1 by about 70 and 130 % for DSCA and MSCA, respectively, upon Ca2+ saturation. However, a significant change in r2 was obtained for DSCA (360 %), while MSCA changed with the same trend as for r1 (140 %). Experiments performed in BEM indicated a change in r2/r1 ratio of over 100 % upon Ca2+ saturation on both temperatures. DLS measurements demonstrate an increment of the DSCA diameter upon addition of Ca2+ (5.4±0.5 - 8.3±0.3 nm). Analysis of MR images for DSCA showed that comparable SNR values could be obtained for RARE (7-10) and bSSFP (8-12), (same NA, acquisition times 10.0 and 1.4 s, respectively). Consequently, CNR normalized per acquisition time (CNRt) obtained for bSSFP was two and half or over six times higher than for RARE or FLASH, respectively. Lastly, comparing new methodology with conventional T1w imaging (using MSCA), CNRt exhibited a 4-fold increment.It is well established that the main contribution to the Ca-induced relaxivity increment for MSCA is due to the change of the hydration number. Here we have succeeded to cause an additional effect on local rotation of the GdDO3A units [4], by coupling the monomeric units to a dendrimer and employing the interaction of this system with Ca2+, thus making this effect suitable for high magnetic fields [5]. Relaxometric titrations demonstrated that longitudinal and transversal relaxation times of DSCA change as a function of [Ca2+] with different magnitudes. Moreover, experiments made in BEM suggest an excellent compensation of the undesired negative effect of anions by this ratiometric approach [2]. When compared to MSCA, DSCA results in i) smaller increase of r1; ii) much greater increase of r2, which might be useful for T2w imaging; iii) dramatic change in r2/r1 ratio as a function of Ca2+, thus allowing ratiometric monitoring [6]. Diffusion studies proved dramatic change in DSCA diameter upon Ca2+ saturation. This clearly explains the observed r2 behaviour of DSCA [7], and advocate towards slower in vivo diffusion and more stable MR signal [1]. MRI using bSSFP demonstrated that high SNR with significant contrast could be obtained with acquisition times less than 1 second. Accordingly, obtained CNRt with DSCA was significantly higher when compared to current small sized SCAs and conventional imaging methodologies. Thus, this approach demonstrates a great potential for tracking biological processes by means of functional MRI, including brain activity.Herein presented results show the immense potential of a new ratiometric method based on nano-sized bioresponsive MRI agents for monitoring dynamic processes. This proof-of-concept study was demonstrated with a Ca-sensitive MR contrast agent, whose importance in neuroscience may be tremendous. We stress that this technique provides an immense SNR in subsecond range, thus envisaging many opportunities for studying various biological processes with fast kinetics.