Tuberculomas can occasionally masquerade as high-grade gliomas (HGG). Evidence from magnetisation transfer (MT) imaging suggests that there is lower protein content in the tuberculoma microenvironment. Building on the principles of chemical exchange saturation transfer and MT, amide proton transfer (APT) imaging generates tissue contrast as a function of the mobile amide protons in tissue’s native peptides and intracellular proteins. This study aimed to further the understanding of tuberculomas using APT and to compare it with HGG.
Method
Twenty-two patients (n = 8 tuberculoma; n = 14 HGG) were included in the study. APT was a 3D turbo spin-echo Dixon sequence with inbuilt B0 correction. A two-second, 2 μT saturation pulse alternating over transmit channels was applied at ±3.5 ppm around water resonance. The APT-weighted image (APTw) was computed as the MT ratio asymmetry (MTRasym) at 3.5 ppm. Mean MTRasym values in regions of interest (areas = 9 mm2; positioned in component with homogeneous enhancement/least apparent diffusion coefficient) were used for the analysis.
Results
MTRasym values of tuberculomas (n = 14; 8 cases) ranged from 1.34% to 3.11% (M = 2.32 ± 0.50). HGG (n = 17;14 cases) showed MTRasym ranging from 2.40% to 5.70% (M = 4.32 ± 0.84). The inter-group difference in MTRasym was statistically significant (p < 0.001). APTw images in tuberculomas were notable for high MTRasym values in the perilesional oedematous-appearing parenchyma (compared to contralateral white matter; p < 0.001).
Conclusion
Tuberculomas demonstrate lower MTRasym ratios compared to HGG, reflective of a relative paucity of mobile amide protons in the ambient microenvironment. Elevated MTRasym values in perilesional parenchyma in tuberculomas are a unique observation that may be a clue to the inflammatory milieu.
SusluHTBozbugaMBayindirC.Cerebral tuberculoma mimicking high grade glial tumor. Turk Neurosurg2011;
21: 427–429.
2.
PengJOuyangYFangW-D, et al.
Differentiation of intracranial tuberculomas and high grade gliomas using proton MR spectroscopy and diffusion MR imaging. Eur J Radiol2012;
81: 4057–4063.
3.
DashCSinglaRGargK, et al.
Hypothalamic chiasmatic tuberculoma mimicking glioma. Childs Nerv Syst2016;
32: 233–235.
4.
KimJ-KJungT-YLeeK-H, et al.
Radiological follow-up of a cerebral tuberculoma with a paradoxical response mimicking a brain tumor. J Korean Neurosurg Soc2015;
57: 307.
5.
AlgahtaniHAAldarmahiAAAlgahtaniAY, et al.
Tumour-like presentation of central nervous system tuberculosis: a retrospective study in Kingdom of Saudi Arabia. J Taibah Univ Med Sci2014;
9: 143–150.
MukherjeeSDasRBegumS.Tuberculoma of the brain – a diagnostic dilemma: magnetic resonance spectroscopy a new ray of hope.J Assoc Chest Phys2015;
3: 3.
8.
BernaertsAVanhoenackerFMParizelPM, et al.
Tuberculosis of the central nervous system: overview of neuroradiological findings. Eur Radiol2003;
13: 1876–1890.
SchallerMAWickeFFoerchC, et al.
Central nervous system tuberculosis: etiology, clinical manifestations and neuroradiological features. Clin Neuroradiol2019;
29: 3–18.
11.
ParryAHWaniAHShaheenFA, et al.
Evaluation of intracranial tuberculomas using diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS) and susceptibility weighted imaging (SWI). Br J Radiol2018;
91: 20180342.
12.
MoralesHAlfaroDMartinotC, et al.
MR spectroscopy of intracranial tuberculomas: a singlet peak at 3.8 ppm as potential marker to differentiate them from malignant tumors. Neuroradiol J2015;
28: 294–302.
13.
GuptaRKKathuriaMKPradhanS.Magnetization transfer MR imaging in CNS tuberculosis. Am J Neuroradiol1999;
20: 867–875.
14.
HarisMGuptaRKHusainM, et al.
Assessment of therapeutic response in brain tuberculomas using serial dynamic contrast-enhanced MRI. Clin Radiol2008;
63: 562–574.
15.
ChatterjeeSSainiJKesavadasC, et al.
Differentiation of tubercular infection and metastasis presenting as ring enhancing lesion by diffusion and perfusion magnetic resonance imaging. J Neuroradiol2010;
37: 167–171.
16.
GuptaR.Magnetization transfer MR imaging in central nervous system infections. Ind J Radiol Imag2002;
12: 51.
17.
GuptaRKHarisMHusainN, et al.
Relative cerebral blood volume is a measure of angiogenesis in brain tuberculoma. J Comput Assist Tomogr2007;
31: 335–341.
18.
PatkarDNarangJYanamandalaR, et al.
Central nervous system tuberculosis: pathophysiology and imaging findings. Neuroimaging Clin N Am2012;
22: 677–705.
19.
ZhouJHeoH-YKnutssonL, et al.
APT-weighted MRI: techniques, current neuro applications, and challenging issues: APTw MRI for neuro applications. J Magn Reson Imaging2019;
50: 347–364.
20.
SakataAOkadaTYamamotoY, et al.
Addition of amide proton transfer imaging to FDG-PET/CT improves diagnostic accuracy in glioma grading: a preliminary study using the continuous net reclassification analysis. AJNR Am J Neuroradiol2018;
39: 265–272.
21.
ChoiYSAhnSSLeeS-K, et al.
Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume. Eur Radiol2017;
27: 3181–3189.
22.
RazekAATalaatMEl-SerougyL, et al.
Differentiating glioblastomas from solitary brain metastases using arterial spin labeling perfusion- and diffusion tensor imaging-derived metrics.World Neurosurg2019;
127: e593–598.
23.
RazekAAEl-SerougyLAbdelsalamM, et al.
Differentiation of primary central nervous system lymphoma from glioblastoma: quantitative analysis using arterial spin labeling and diffusion tensor imaging.World Neurosurg2019;
123: e303–309.
24.
El-SerougyLAbdel RazekAAEzzatA, et al.
Assessment of diffusion tensor imaging metrics in differentiating low-grade from high-grade gliomas. Neuroradiol J2016;
29: 400–407.
25.
RazekAATalaatMEl-SerougyL, et al.
Clinical applications of arterial spin labeling in brain tumors. J Comput Assist Tomogr2019;
43: 525–532.
26.
LouisDNPerryAReifenbergerG, et al.
The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol2016;
131: 803–820.
27.
TogaoOKeuppJHiwatashiA, et al.
Amide proton transfer imaging of brain tumors using a self-corrected 3D fast spin-echo Dixon method: comparison with separate B0 correction. Magn Reson Med2017;
77: 2272–2279.
28.
TogaoOHiwatashiAKeuppJ, et al.
Amide proton transfer imaging of diffuse gliomas: effect of saturation pulse length in parallel transmission-based technique. PLoS One2016;
11: e0155925.
29.
ZhouJ.Amide proton transfer imaging of the human brain.Methods Mol Biol2011;
711: 227–237.
30.
WardKMAletrasAHBalabanRS.A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). J Magn Reson2000;
143: 79–87.
31.
KamimuraKNakajoMYoneyamaT, et al.
Amide proton transfer imaging of tumors: theory, clinical applications, pitfalls, and future directions. Jpn J Radiol2019;
37: 109–116.
32.
ZhouJPayenJ-FWilsonDA, et al.
Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med2003;
9: 1085–1090.
33.
ZhengYWangXZhaoX.Magnetization transfer and amide proton transfer MRI of neonatal brain development. Biomed Res Int2016;
2016: 3052723.
34.
TogaoOHiwatashiAYamashitaK, et al.
Grading diffuse gliomas without intense contrast enhancement by amide proton transfer MR imaging: comparisons with diffusion- and perfusion-weighted imaging. Eur Radiol2017;
27: 578–588.
35.
JiangSYuHWangX, et al.
Molecular MRI differentiation between primary central nervous system lymphomas and high-grade gliomas using endogenous protein-based amide proton transfer MR imaging at 3 Tesla. Eur Radiol2016;
26: 64–71.
36.
SuCZhaoLLiS, et al.
Amid proton transfer (APT) and magnetization transfer (MT) MRI contrasts provide complimentary assessment of brain tumors similarly to proton magnetic resonance spectroscopy imaging (MRSI). Eur Radiol2019;
29: 1203–1210.
37.
ZhangHKangHZhaoX, et al.
Amide proton transfer (APT) MR imaging and magnetization transfer (MT) MR imaging of pediatric brain development. Eur Radiol2016;
26: 3368–3376.
38.
KökoǧluE.RNA, DNA and total protein levels in subcellular fractions of human brain tumors. Cancer Lett1987;
34: 67–71.
39.
LiJZhuangZOkamotoH, et al.
Proteomic profiling distinguishes astrocytomas and identifies differential tumor markers. Neurology2006;
66: 733–736.
40.
HobbsSKShiGHomerR, et al.
Magnetic resonance image-guided proteomics of human glioblastoma multiforme. J Magn Reson Imaging2003;
18: 530–536.
41.
HoweFABartonSJCudlipSA, et al.
Metabolic profiles of human brain tumors using quantitative in vivo 1H magnetic resonance spectroscopy. Magn Reson Med2003;
49: 223–232.
42.
SuCLiuCZhaoL, et al.
Amide proton transfer imaging allows detection of glioma grades and tumor proliferation: comparison with Ki-67 expression and proton MR spectroscopy imaging. Am J Neuroradiol2017;
38: 1702–1709.
43.
YanKFuZYangC, et al.
Assessing amide proton transfer (APT) MRI contrast origins in 9 L gliosarcoma in the rat brain using proteomic analysis. Mol Imaging Biol2015;
17: 479–487.
44.
KhatriGDKrishnanVAntilN, et al.
Magnetic resonance imaging spectrum of intracranial tubercular lesions: one disease, many faces. Pol J Radiol2018;
83: e524–535.
45.
TorresCRiascosRFigueroaR, et al.
Central nervous system tuberculosis. Top Magn Reson Imaging2014;
23: 173–189.
46.
RockRBOlinMBakerCA, et al.
Central nervous system tuberculosis: pathogenesis and clinical aspects. Clin Microbiol Rev2008;
21: 243–261.
47.
Kleinschmidt-DeMastersBKBeckhamJDTylerKL.23 – Infections and inflammatory disorders. In: Perry A and Brat DJ (eds) Practical surgical neuropathology: a diagnostic approach. 2nd ed.Philadelphia:
Elsevier, 2018, pp.547–579.
48.
GuptaRKPandeyRKhanEM, et al.
Intracranial tuberculomas: MRI signal intensity correlation with histopathology and localised proton spectroscopy. Magn Reson Imaging1993;
11: 443–449.
49.
GuptaRKKumarS.Central nervous system tuberculosis. Neuroimaging Clin N Am2011;
21: 795–814, vii–viii.
50.
KimTKChangKHKimCJ, et al.
Intracranial tuberculoma: comparison of MR with pathologic findings. AJNR Am J Neuroradiol1995;
16: 1903–1908.
51.
GuptaRKHusainNKathuriaMK, et al.
Magnetization transfer MR imaging correlation with histopathology in intracranial tuberculomas. Clin Radiol2001;
56: 656–663.
52.
GuptaRKPrakashMMishraAM, et al.
Role of diffusion weighted imaging in differentiation of intracranial tuberculoma and tuberculous abscess from cysticercus granulomas – a report of more than 100 lesions. Eur J Radiol2005;
55: 384–392.
53.
WenZHuSHuangF, et al.
MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast. Neuroimage2010;
51: 616–622.
54.
YuHLouHZouT, et al.
Applying protein-based amide proton transfer MR imaging to distinguish solitary brain metastases from glioblastoma. Eur Radiol2017;
27: 4516–4524.
55.
DebnathAGuptaRKSinghA.Evaluating the role of amide proton transfer (APT)–weighted contrast, optimized for normalization and region of interest selection, in differentiation of neoplastic and infective mass lesions on 3T MRI.Mol Imaging Biol2020;
22: 384–396.
56.
TogaoOYoshiuraTKeuppJ, et al.
Amide proton transfer imaging of adult diffuse gliomas: correlation with histopathological grades. Neuro-Oncology2014;
16: 441–448.
57.
ParkJEKimHSParkKJ, et al.
Pre- and posttreatment glioma: comparison of amide proton transfer imaging with MR spectroscopy for biomarkers of tumor proliferation. Radiology2016;
278: 514–523.
58.
JeongH-KHanKZhouJ, et al.
Characterizing amide proton transfer imaging in haemorrhage brain lesions using 3T MRI. Eur Radiol2017;
27: 1577–1584.
59.
WangMHongXChangC-F, et al.
Simultaneous detection and separation of hyperacute intracerebral hemorrhage and cerebral ischemia using amide proton transfer MRI: MRI detection of intracerebral hemorrhage. Magn Reson Med2015;
74: 42–50.
60.
RayKJSimardMALarkinJR, et al.
Tumor pH and protein concentration contribute to the signal of amide proton transfer magnetic resonance imaging. Cancer Res2019;
79: 1343–1352.
61.
RossBDHigginsRJBogganJE, et al.
31P NMR spectroscopy of the in vivo metabolism of an intracerebral glioma in the rat. Magn Reson Med1988;
6: 403–417.
