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. 2025 Nov;12(11):2305-2316.
doi: 10.1002/acn3.70161. Epub 2025 Aug 16.

Quantitative Iron Measurements in the Basal Ganglia of NBIA Patients Using QSM: Insights From a Tertiary Center

Özge Uygun  1 , Alpay Özcan  2 , Fuat Kaan Aras  3 , Evrim Bozdemir  4 , Sibel Uğur İşeri  5 , Koray Kırımtay  6 , Arzu Karabay  6 , Murat Gültekin  7 , Nihan Hande Akçakaya  8 , Orkhan Mammadov  9 , Gülay Kır  10 , Dilek İnce Günal  11 , Neşe Tuncer  12 , Fatma Betül Özdilek  13 , Banu Özen Barut  14 , Ercan Köse  15 , Hülya Apaydın  1 , Asuman Ali  16 , Sultan Çağırıcı  17 , Pınar Topaloğlu  18 , Alp Dinçer  19 , Zuhal Yapıcı  18
Affiliations

Quantitative Iron Measurements in the Basal Ganglia of NBIA Patients Using QSM: Insights From a Tertiary Center

Özge Uygun et al. Ann Clin Transl Neurol. 2025 Nov.

Abstract

Objective: Neurodegeneration with brain iron accumulation (NBIA) comprises rare genetic disorders characterized by predominantly extrapyramidal symptoms and iron deposition in the basal ganglia. Conventional magnetic resonance imaging (MRI) detects qualitative changes but cannot accurately quantify iron accumulation. Quantitative susceptibility mapping (QSM) allows precise in vivo quantification of iron, providing insight into the pathophysiology of the disease.

Methods: We studied 27 genetically confirmed NBIA patients and 11 age-matched healthy controls using susceptibility-weighted imaging (SWI) on a 3 Tesla MRI scanner. Basal ganglia regions of interest (ROIs) were manually delineated and QSM values were extracted.

Results: Sixteen NBIA patients and 11 controls were analyzed. QSM showed significantly higher iron in the globus pallidus (GP) (p = 0.008), with PKAN patients showing a 2.5-fold increase in GP iron (p = 0.001). MPAN patients showed 2.5 times higher iron in both GP and substantia nigra (SN). A GP iron level > 0.1133 ppm increased the likelihood of PKAN 18-fold. Atypical PKAN cases had 2.5 times higher SN iron levels compared to classic cases.

Interpretation: QSM is a sensitive and noninvasive tool for detecting and quantifying iron accumulation in NBIA. The GP consistently showed the highest susceptibility values across subtypes, emphasizing its significant role in disease pathology. Distinct patterns of iron deposition in different NBIA subtypes may reflect subtype-specific mechanisms with diagnostic and therapeutic relevance. Age-related susceptibility changes were found to be significant, reinforcing the need to account for age when interpreting QSM data. More importantly, QSM may serve as a candidate biomarker for longitudinal disease monitoring in future clinical trials targeting disease-modifying therapies in NBIA.

Keywords: Kufor Rakeb syndrome; MPAN; MRI; NBIA; PKAN; PLAN; QSM; basal ganglia; iron accumulation.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Comparison of QSM of the basal ganglia of healthy control and PKAN patient.
FIGURE 2
FIGURE 2
Quantitative comparison of iron levels in (A) globus pallidus and (B) putamen nuclei between NBIA patients and healthy controls. Susceptibility values are expressed in parts per million (ppm). Statistical significance, GP (p = 0.008), Putamen (p = 0.015).
FIGURE 3
FIGURE 3
Quantitative comparison of iron levels in (A) globus pallidus and (B) nucleus caudatus between PKAN patients and healthy controls. Susceptibility values are expressed in parts per million (ppm). Statistical significance, GP (p = 0.001), NC (p = 0.026).
FIGURE 4
FIGURE 4
Quantitative comparison of iron levels in (A) nucleus caudatus between patients with homozygous and heterozygous mutations and (B) substantia nigra between typical and atypical PKAN patients. Susceptibility values are expressed in parts per million (ppm). Statistical significance, NC (p = 0.036), SN (p = 0.024).
FIGURE 5
FIGURE 5
Quantitative comparison of iron levels in (A) globus pallidus and (B) substantia nigra between MPAN patients and healthy controls. Susceptibility values are expressed in parts per million (ppm). Statistical significance, GP (p = 0.005), SN (p = 0.036).
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