{'fraction_non_alphanumeric': 0.02845699831365936, 'fraction_numerical': 0.002529510961214165, 'mean_word_length': 5.57202216066482, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Editorial for “Amide Proton Transfer MRI Could Be Used to Evaluate the Pathophysiological Status of White Matter Hyperintensities”

Editorial for “Amide Proton Transfer MRI Could Be Used to Evaluate the Pathophysiological Status of White Matter Hyperintensities” Cerebral small vessel disease (cSVD) is a group of disorders causing sudden or progressive stenosis, occlusion or rupture of small vessels of the brain, which result in various lesions on pathological and neuroimaging examinations. At MRI, typical cSVD-related lesions are white matter hyperintensities (WMHs) of presumed vascular origin, lacunar infarcts, microbleeds, superficial siderosis, enlarged perivascular spaces, and microinfarcts. Most cSVD is sporadic, likely related to advancing age, hypertension, and other vascular risk factors. Other causes are cerebral amyloid angiopathy, inflammatory/ autoimmune conditions (eg primitive or systemic vasculitis) and rare genetic diseases (especially cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). From a clinical point of view, cSVD is often silent, but strategically located lacunar infarcts and intracerebral hemorrhages typically present with stroke. Moreover, a higher burden of cSVD-related lesions is associated with cognitive impairment, gait and balance problems, mood disorders, increased risk of stroke, and worse outcome after stroke. From an MRI point of view, WMHs are a common sign of cSVD, but they are not specific, being found in several inflammatory-demyelinating disorders (eg multiple sclerosis) and other neurological conditions (eg neurodegenerative dementias). The presence of WMH on MRI reflects different pathological substrates, including demyelination, axonal loss, and gliosis. Some features of WMH on conventional MRI sequences, such as location, shape, pattern of contrast enhancement, and evolution over time, can help differentiating lesions due to inflammatory disorders from those related to cSVD, but the separation is not always straightforward. Advanced MRI techniques are showing great promise in aiding the differential diagnosis of WMH, for instance, through the investigation of the central vein sign, which seems to be characteristic of multiple sclerosis lesions. These techniques are also contributing to highlight the mechanisms related to the formation and progression of cSVD-related WMH. A diffusion-tensor MRI study showed that altered microstructural integrity precedes conversion of the normal-appearing white matter into WMH and continuously declines over time within WMH, suggesting a continuous process of white matter integrity disruption. cSVDrelated WMH also affect structural connectivity, leading to cognitive deficits. Finally, several longitudinal studies have demonstrated volume reduction of some WMH, possibly due to changes in water content inside the lesions. Against this background, amide proton transfer (APT) imaging is a promising advanced MRI technique for the study in vivo of tissue biophysics, especially in hypoxic–ischemic conditions. This pulse sequence is based on the signal generated by the proton exchange between the amide protons of mobile proteins and peptides in cells and free water. A single measure is derived from this sequence, named “APT ratio” or “APT-weighted measure” (APTw), in a given region of interest. This metric is mainly dependent on intracellular protein content and pH, which are altered in hypoxic–ischemic conditions, mainly due to tissue loss and acidosis. In this issue of JMRI, Guo et al report on the application of APT to the study of cSVD-related WMH. Patients were selected among stroke-free community residents (age ≥ 40 years) with no contraindication to MRI, no medical or neurological diseases (apart from previously recognized cSVD). The authors found significant differences of APT signals in cSVD-related WMH, according to their location (periventricular vs. diffuse) and grade, which was rated with the commonly used Fazekas grading scale (grades 1–3 with increasing severity). Interestingly, they found a significant decline in WMH APTw in grade 1 lesions vs. healthy controls, and an increase thereafter (grade 2 vs. grade 1, and grade 3 vs. grade 2), returning to values similar to healthy controls in grade 3 lesions. Since protein content is bound not to be significantly altered within WMH, contrary to brain tumors or infarcts, these reported abnormalities are likely to be caused by pH modifications. Accordingly, the authors formulated an interesting hypothesis that grade 1 and 2 WMH may show impaired APT due to chronic acidosis, related in turn to chronic hypoperfusion. Thus, this study supports previous data on the progressive nature of WMH, and