Nutrition in early life has an impact on white matter (WM) development in preterm-born babies. Quantitative analysis of pixel brightness intensity (PBI) on cranial ultrasound (CUS) scans has shown a great potential in the evaluation of periventricular WM echogenicity in preterm newborns. We aimed to investigate the employment of this technique to objectively verify the effects of parenteral nutrition (PN) on periventricular WM damage in preterm infants. Prospective observational study including newborns with gestational age at birth ≤32 weeks and/or birth weight ≤1500 g who underwent CUS examination at term-equivalent age. The echogenicity of parieto-occipital periventricular WM relative to that of homolateral choroid plexus (RECP) was calculated on parasagittal scans by means of quantitative analysis of PBI. Its relationship with nutrient intake through enteral and parenteral routes in the first postnatal week was evaluated. The study included 42 neonates for analysis. We demonstrated that energy and protein intake administered through the parenteral route positively correlated with both right and left RECP values (parenteral energy intake vs. right RECP: r = 0.413, p = 0.007; parenteral energy intake vs. left RECP: r = 0.422, p = 0.005; parenteral amino acid intake vs. right RECP: r = 0.438, p = 0.004; parenteral amino acid intake vs. left RECP: r = 0.446, p = 0.003). Multivariate linear regression analysis confirmed these findings. Quantitative assessment of PBI could be considered a simple, risk-free, and repeatable method to investigate the effects of PN on WM development in preterm neonates.