• MRI
• quantitative relaxometry
• T1 mapping
• ultra-high field

Magnetic Resonance Imaging (MRI) is a powerful medical imaging tool whose main benefits are its
non-invasiveness, thanks to the usage of non-ionizing radiation, and its versatility, which allows it
to probe different physical tissue properties obtaining morphological, functional and metabolic
information. In the last decades the introduction of Ultra High Field (UHF) scanners (i.e. with a
magnetic field strength ≥ 7T) yielded an improvement in signal-to-noise ratio (SNR) enabling
imaging with higher spatial resolution and allowing the delineation of small anatomical structures
and subtle pathology. Despite its advantages, conventional MRI is qualitative, meaning that the
diagnosis is based on the visual detection of hypo- and hyper-intensities of the lesions with respect
to the surrounding areas, but not on a direct measurement of a physical tissue property.
The diagnostic power of MRI can be further improved by quantitative techniques, such as
relaxometry, that is the measurements of the tissue relaxation times. In particular, the longitudinal
relaxation time T1 is related to several biomarkers such as myelination, iron deposition, contrast
agent uptake and blood perfusion. However, T1 relaxometry typically requires long acquisition
times such as in Inversion Recovery method, making it unsuitable to clinical applications. In this
context the Variable Flip Angle (VFA) method allows quantitative measurements of T1 in a short
scan time based on the combination of readily available vendor-provided sequences. Potential
pitfalls of this approach concern its sensitivity to several factors such as field inhomogeneities and
magnetization transfer (MT) effect. MT is a process that involves an energy exchange between the
nuclear spins of water and the macromolecules present within the sample. MT modifies the
apparent T1 and its effect can be modulated by different settings of the acquisition protocol.
The purpose of this thesis was the implementation and the characterization of a VFA technique in
order to obtain fast quantitative T1 maps of the human brain at 7T and evaluate MT effect in T1
quantification. The work was performed at the Laboratory of Medical Physics and Magnetic
Resonance of the IRCCS Stella Maris Foundation and at the IMAGO7 research center in Pisa.
The first part of the thesis presents an overview of the theoretical framework of this work,
describing the main physical principles at the basis of Nuclear Magnetic Resonance (NMR) and
MRI, also discussing the advantages and drawbacks of UHF MRI (Chapters 1-2). We then
introduced the main techniques used for T1 relaxometry (Chapter 3), exploring the differences and
benefits of each method.
The experimental work is presented in the second part of the thesis. In Chapter 4 a VFA protocol
was designed and tested in a phantom experiment. The T1 map reconstruction pipeline was
implemented and refined accounting for different confounding effects such as excitation field
inhomogeneities and modeling the effect of finite duration of the spin excitation. Then, the
acquisition protocol was modified to study the effect of the MT on T1 quantification. Finally, the
accuracy of the T1 estimation via VFA was assessed via a comparison with the Inversion Recovery
(IR), which is considered as the gold standard method for T1 relaxometry.
In Chapter 5, the results of the in-vivo validation on the brain of a healthy volunteer of the
implemented VFA method are presented. In particular, the MT effect was studied throughout the
acquisition and analysis of different sets of imaging parameters. A different impact of MT effect
was found depending on the microstructure of the brain tissue of interest. Then, an accuracy
assessment was performed.
In conclusion, a VFA technique for T1 in-vivo estimation at 7T was implemented, characterized
and optimized, with a scan time feasible for in vivo acquisition, potentially facilitating the translation
of this quantitative technique to a clinical setting.