Magnetic resonance in neuro-oncology: Achievements and challenges - Signal Processing in MRS with Biomedical Applications - page 257

particle radiation may be considered. Accurate grading of intracerebral neo
plasms can be very di cult, due especially to tumor heterogeneity. For this
reason, brain biopsy may not provide the definitive answer, besides being as
sociated with substantial morbidity, as noted. Thus, there has been interest
in using in vivo MRSI with full volumetric coverage for grading brain tumors.
Indeed, MRSI has been helpful in this endeavor. For example, it is often
found that higher grade gliomas show the greatest elevation in the ratios of
choline to creatine and choline to NAA [211, 242]. In a study of fifteen pa
tients with grade II gliomas, seventeen patients with grade III and seventeen
patients with grade IV, the maximum choline to NAA ratio was found to be
a much better indicator of glioma tumor grade than were either contrast en
hancement or T 2 hyperintensity on MRI [242]. In another study [243], among
eighteen patients with Grade II or Grade III gliomas, the choline to creatine
ratios were found to best distinguish these two grades. A choline to creatine
ratio > 2.33 was reported to be the most accurate for detecting nine high
grade malignancies from a total of twentytwo patients with oligodendroglial
tumors [244]. A choline to creatine ratio > 1.55 identified high grade brain
tumors with a sensitivity of 92% and specificity of 80% in another study which
included twentyfour patients [245].
Lactate levels are often found to parallel tumor grade [211, 240], [246]-
[248]. This is biologically plausible, since the appearance of lactate caused by
anaerobic glycolysis is the main metabolic pathway for glucose utilization by
anaplastic brain tumors [249]. Histopathologic evidence is also corroborative,
in that a positive correlation has been reported between the height of the lac
tate peak and the degree of heterogeneity of the nuclear roundness factor in
anaplastic gliomas [250]. Lactate to creatine ratios provided the best distinc
tion between Grade III and Grade IV gliomas in the earliercited study [243],
which included ten patients with these two grades of tumor. Necrosis is a
frequent characteristic of highergrade brain tumors. The spectra of glioblas
tomas are reportedly often dominated by large lipid - lactate resonances [251].
Several investigations show that the presence or greater concentration of lipids
is associated with highergrade intracerebral tumors [232, 239, 242, 252, 253].

8.1.3.1 Grading of pediatric brain tumors

Magnetic resonance spectroscopy and spectroscopic imaging have also been
helpful for assessing brain tumor grade in the pediatric population. Low to
tal choline was found to be associated with low proliferative tumors in an
investigation of fourteen children with diffuse brainstem gliomas [254]. High
choline levels have been reported to be associated with highgrade brain tu
mors among children [255]. In a study [256] of twentyfour children with
brain tumors, those who responded to chemotherapy or RT also showed sig
nificantly lower choline and higher total creatine. Lipids and lactate were also
lower among the responders than among those treated only by surgery or who
did not respond to treatment. The only metabolite to independently predict