Invasive Endotyping of Angina Pectoris with Nonobstructive Coronary Arteries.

Alpha-synucleinopathies are disabling neurodegenerative diseases, with the most common clinical phenotypes being Parkinson's disease (PD) and dementia with Lewy Bodies (DLB). Neurodegeneration in alpha-synucleinopathies is typically assessed by evaluating nigrostriatal pathway dysfunction using single photon emission computed tomography (SPECT) with [I]-ioflupane (DaT-SPECT) which serves as the gold standard for in vivo evaluation of the nigrostriatal pathway. Less invasive neuroimaging techniques to evaluate nigrostriatal pathway are currently under validation in research settings. For example, iron sensitive MRI can provide with promising markers of neurodegeneration to assess the substantia nigra (SN); however, this approach is still considered investigational by the recent biological research frameworks, with few studies exploring its use in prodromal alpha-synucleinopathies. A visually assessable radiological marker of SN pathology is the loss of the physiological dorsal nigral hyperintensity (DNH), which is caused by iron accumulation. DNH is typically evaluated using magnetic resonance susceptibility-weighted imaging (SWI) a technique combining the magnitude and phase images obtained with a gradient echo (GRE) acquisition. In particular, the SWI reconstruction uses the signal phase, reflecting local field inhomogeneities originating from biological tissues’ magnetic susceptibility, to enhance the T2*-weighted contrast embedded in the conventional magnitude images. This way, the hypo-intensity of paramagnetic tissues, such as those with increased iron concentration, is emphasized. The normal appearance of the DNH in SWI at the expected anatomical location of nigrosome 1 (N1) at level of the midbrain level is known as the swallow tail sign. The assessment of the swallow tail sign using SWI in MRI scanners operating at 3T showed excellent sensitivity (94.6%) and specificity (94.4%) in identifying patients with overt PD but only fair sensitivity (63%) and specificity (79%) in identifying DLB. Few studies investigated iron sensitive MRI in the prodromal phases, such as in idiopathic/isolated REM sleep behavior disorder (iRBD), showing abnormal N1 imaging in about 60% of iRBD cases. The identification of reliable biomarkers able to assess substantia nigra neurodegeneration since prodromal alpha-synucleinopathy stage is of paramount importance in the light of the new framework for a biological definition of PD, as well as upcoming clinical trials testing disease modifying drugs. One known limitation of SWI is that it directly relies on local field inhomogeneities to emphasize magnetic susceptibility effects: such field inhomogeneities spatially extends beyond the tissues that generate them, therefore the image feature emphasized by SWI do not precisely co-localize with the underlying anatomy. An improved implementation of SWI, namely susceptibility mapping weighted imaging (SMWI), relies on the same acquisition as SWI, but employs a refined reconstruction pipeline including an image processing step to remove the non-local phase perturbations by a deconvolution operation. Therefore, SMWI results in improved susceptibility contrast and reduced “blooming” artifact and has been proved to provide enhanced N1 anatomical depiction and visibility at 3T when compared to conventional SWI. A recent multi-centric study involving patients with degenerative and non-degenerative forms of parkinsonisms reported no significant difference between SMWI and DaTPET diagnostic performance. SMWI has never been tested in prodromal stages of alpha-synucleinopathies and we hypothesized that SMWI would enable neuroradiologists detecting an altered appearance of the substantia nigra not only in the overt forms of alpha-synucleinopathy, but also the prodromal stages. The aim of the present project was to confirm this hypothesis by visually evaluating the SMWI swallow tail sign representations of patients along the prodromal to overt alpha-synucleinopathy continuum. For comparison, we included a group of healthy subjects (HC) and patients with Alzheimer's disease (AD). Moreover, we assessed the relationship between the SMWI visual evaluation of the swallow tail sign and quantitative susceptibility mapping (QSM) semi-quantification of iron content in the substantia nigra to further validate this imaging marker. Finally, we aimed to compare the SMWI assessment with DaT-SPECT results.