Method for diagnosing neurological, neurodegenerative and psychiatric diseases by magnetic resonance imaging using contrast agents with high magnetic susceptibility and extended plasma half life

A method for measuring or depicting in a spatially and timely resolved manner the changes in regional Cerebral blood Volume (rCBV mapping) associated with changes in neurotransmitter activity exploiting the susceptibility contract effect, employing the compartmentalization of susceptibility contrast agents in the vasculature and of the constant or nearly constant concentration in blood over time comprising the steps of:

• (a) administering to said patient a drug eliciticiting an MRI detectable hemodynamic response;
• (b) administering to said patient an MRI ferromagnetic, antiferromagnetic or superparamagnetic contrast agent with high magnetic susceptibility and
• (c) measuring, in a spatially and temporally resolved manner, relative Cerebral Blood Volume (rCBV) changes associated to neuronal activating using T2- or T2*weighted MRI scans at the equilibrium distribution of said contrast agent, and relating the changes in signal intensity (SI) in T=2*- or T2-weighted MR images to changes of rCBV.

A method for mapping rCBV changes associated with neurotransmittcr activity using T2- or T=2*-weighted sequences using a ferromagnetic, antiferromagnetic or superparamagnetic susceptibility contrast agents to determine transversal apparent relaxation rates R2 and R2*, wherein T2 and T2* are monoexponential time constants and R2 and R2* are transversal relaxation rates of brain tissue, apparent relaxivity meaning the time constant for the decay of transversal magnetization obtained assuming monoexponential decay after excitation by radiofrequency, using the relation ΔRR2*=−(InSt/S0)/TE, where ΔR2* is the change in relaxation rate St is the signal intensity at time t after contrast administration, S0 is the precontrast signal intensity baseline and TE is the Echo Time, and relating the approximately linear relationship between ΔR2* and agent concentration in tissue to determine relative changes in blood volume, as(−Vt)/V0=(ΔR2*(t)/ΔRR2*(0))−1, where V0 is the value for rCBV at rest and Vt is the value for rCBV at time t after contrast administration.

A method for assessing changes in neurotransmitter and neuroreceptor activity as a metabolic response to diagnostic challenge or therapeutic treatment in a patient with suspected or already diagnosed mental illness of psychiatric, neurodegenerative or neurological nature, said method comprising the steps of

• (a) inducing neuronal activation in the patient by administering a neuronal activator eliciting a hemodynamic response,
• (b) MR Imaging said patient to assess changes in the patient's regional cerebral blood volume using a negative blood and contrast agent, and thereafter
• (c) relating to the changes to the patient's condition.