The document discusses the use of perfusion MRI and MR spectroscopy in evaluating brain tumors. It states that perfusion MRI can help estimate tumor grade, guide biopsy to aggressive portions, and better delineate tumor margins compared to conventional MRI. MR spectroscopy can detect metabolic alterations to help characterize tumors and differentiate them from other conditions like abscesses. Together, perfusion MRI and MR spectroscopy provide physiological and metabolic information complementary to anatomical MRI for diagnosing and monitoring brain tumors.

1. Perfusion and MR spectroscopy of brain tumour.
Dr/ ABD ALLAH NAZEER. MD.

2. Conventional magnetic resonance imaging (MRI) is widely used in the
diagnosis and follow-up of brain tumor patients, owing to its high
sensitivity and exquisite delineation of anatomic relationships.
Nonetheless, conventional MR techniques are often nonspecific and
provide limited information on tumor physiology. Thus, conventional MRI,
which provides a “snapshot” in the time course of contrast enhancement,
is largely inadequate to guide biopsy or treatment of brain tumors.
Indeed, the degree of contrast enhancement of glioblastomas has a
relatively poor correlation with tumor grade and is not a reliable marker
for distinguishing recurrent glioma from radiation necrosis. As novel
therapies for patients with brain tumors are being developed, the role of
imaging has begun to shift to provide information on tumor physiology, as
well as anatomy. Perfusion methods are ideally suited to such
physiological imaging. Multiple studies have shown that perfusion MR
techniques can noninvasively estimate tumor grade preoperatively. This
can in turn help guide stereotactic biopsy, by directing the surgeon to the
most aggressive portions of the tumor. MR perfusion also holds promise in
providing a better delineation of tumor margins than conventional
techniques, which can similarly assist in surgical and radiation planning .

3. Cerebral perfusion is defined as the steady-state delivery of
nutrients and oxygen via blood to brain tissue parenchyma per unit
volume and is typically measured in milliliters per 100 g of tissue per
minute. In perfusion MR imaging, however, the term ‘perfusion’
comprises several tissue hemodynamic parameters (cerebral blood
volume –CBV, cerebral blood flow – CBF, and mean transit time -
MTT) that can be derived from the acquired data. In the evaluation
of intracranial mass lesions, however, CBV appears to be the most
useful parameter.
Perfusion MR imaging methods take advantage of signal
changes that accompany the passage of tracer (most commonly
gadolinium based MR contrast agents) through the Cerebrovascular
system. Perfusion imaging can be performed with techniques based
on dynamic susceptibility contrast (DSC) or based on vascular
permeability. DSC imaging allows approximately 10 MR sections
every second and is ideal for rapid dynamic imaging.

4. MR perfusion is also useful in the follow-up of
brain tumor patients by allowing differentiation
between radiation effects and recurrent tumor.
Perfusion changes also hold promise as surrogate
markers of response to therapy in clinical trials of
newer antiangiogenic pharmaceuticals. In addition to
the “first-pass” dynamic perfusion techniques, which
are well described in the literature, newer, more
prolonged, delayed permeability measurements also
hold great promise for tumor assessment. MR or
computed tomography (CT) perfusion imaging can be
implemented using technology that is widely available
in most contemporary scanners.

11. Underestimation of CBV in the setting of
severe blood-brain barrier breakdown. A)
Axial T1-weighted image (TR 450, TE 20,
matrix 256, 5-mm thick, 6-mm skip, 0.2
mmol/Kg gadolinium at 5 cc/s) shows an
enhancing mass in the right frontal lobe. B)
Axial FLAIR image (TR 10000, TE 126, 5-mm
thick, 6-mm skip) shows significant
associated vasogenic edema, mass effect,
and midline shift. C) Uncorrected CBV map
(perfusion raw data obtained at TR 500, TE
65, 5-mm thick, 6-mm skip, 0.2 mmol/Kg
gadolinium at 5 cc/s) shows low cerebral
blood volume within the lesion (arrow). D)
“K2” first-pass permeability map shows
markedly increased permeability within the
lesion, consistent with severe blood-brain
barrier breakdown. E) Corrected CBV map
shows increased blood volume within the
lesion, consistent with high-grade
neoplasm.

12. Forty-nine-year-old woman with a glioblastoma in the frontal lobes. The
region within the tumour with pronounced signal enhancement is marked
with circle on ASL CBF, DSC rCBF (colour-coded) and DSC rCBV (grey scale).

13. A 22-year-old man with centrally located
glioblastoma multiforme (WHO IV).
A, Tumor shows heterogeneous hyperintensity
with prominent peritumoral edema and/or
tumoral infiltration (arrow) on axial T2-
weighted SE image (2295/90). B, There is a
significant heterogeneous enhancement in
tumoral borders but not in peritumoral area
(arrow) on axial T1-weighted image (583/15).
C, Gradient-echo axial perfusion MR image
(627/30) with rCBV color overlay map shows
both high rCBVT value of 6.58 and rCBVP value of
2.21, which are consistent with HGGT.
Peritumoral increased rCBV (arrow) shows
tumoral infiltration outside the tumoral
margins, which is not perceptible on T2- and
contrast-enhanced T1-weighted images.
D, Time-signal intensity and gamma-variate
fitted curves from tumoral (red), peritumoral
(blue), and normal (purple) areas show
prominent decrease in signal intensity from
tumoral and peritumoral areas, when compared
with signal intensity of normal gray matter.

17. 45-year-old woman presenting with
right hemiparesis and headache. A)
Axial T1-weighted image (TR 450, TE
20, NEX 1, 0.2 mmol/Kg gadolinium
injected at 5 cc/s) shows an
enhancing lesion in the right pons,
midbrain, and thalamus. B) CBV map
shows elevated blood volume within
the lesion, consistent with high-grade
neoplasm (perfusion raw data
obtained at TR 500, TE 65, 5-mm
thick, 6-mm skip, 0.2 mmol/Kg
gadolinium injected at 5 cc/s). C) MR
spectroscopy shows a high choline to
creatine ratio and a decrease in N-acetyl
aspartate, also consistent with
high-grade tumor (single voxel
technique, TR 1500, TE 144). D) FDG-PET
shows foci of high glucose
metabolism within the lesion, also
consistent with high-grade tumor.

18. Low-grade neoplasm. A) Axial FLAIR image (TR 10000, TE 126, 5-mm thick, 6-mm
skip) shows increased T2 signal in the right thalamus and periventricular white
matter with associated mass effect. Post-gadolinium T1-weighted images showed no
associated enhancement (not shown). B) CBV maps (perfusion raw data obtained at
TR 500, TE 65, 5-mm thick, 6-mm skip, 0.2 mmol/Kg gadolinium at 5 cc/s) show no
significant associated increased blood volume within the lesion. Biopsy of lesion
showed to represent a grade 2/4 astrocytoma, a low-grade neoplasm.

20. Oligodendroglioma have high
blood volume irrespective of
grade. A) Unenhanced CT scan
shows a mass in the posterior
left frontal lobe with central
calcification. B) Axial T1-
weighted image (TR 450, TE 20,
NEX 1, 0.2 mmol/Kg gadolinium
at 5 cc/s) shows only trace
enhancement within the lesion.
C) CBV map shows elevated
blood volume within the lesion
(perfusion raw data obtained at
TR 500, TE 65, 5-mm thick, 6-mm
skip, 0.2 mmol/Kg gadolinium at
5 cc/s). Biopsy showed grade 2
oligodendroglioma.

21. A 51-year-old man with cystic METs from
lung carcinoma located in right temporal
lobe. A, Axial T2-weighted spin-echo image
(2295/90), shows hyperintense cystic mass
with peritumoral edema and/or infiltration
(arrows). B, Axial contrast-enhanced T1-
weighted image (583/15) reveals an
irregularly ringlike enhancing mass without
any peritumoral contrast enhancement
(arrows). C, Gradient-echo axial perfusion
MR image (627/30) with rCBV color overlay
map shows a high rCBVT value of 3.05 but
low rCBVP value of 1.05, which is consistent
with METs. No rCBV increase is present on
peritumoral area (arrows). D, Time-signal
intensity and gamma-variate fitted curves
from tumoral (red), peritumoral (green),
and normal (blue) areas show prominent
decrease in signal intensity from tumoral
area. Decreased signal intensity in
peritumoral area is at least equal to or less
than that of normal gray matter.

22. High blood volume in a meningioma. A) Axial T1-weighted image (TR 450, TE
20, NEX 1, 0.2 mmol/Kg gadolinium at 5 cc/s) shows an extra-axial mass with
solid and cystic components, with marked enhancement. B) CBV map shows
marked elevated CBV within the tumor, consistent with high tumor vascularity
(perfusion raw data obtained at TR 500, TE 65, 5-mm thick, 6-mm skip, 0.2
mmol/Kg gadolinium at 5 cc/s). Surgery confirmed a grade 2/4 meningioma.

23. Radiation necrosis. A) Axial T1-weighted
image (TR 450, TE 20, NEX 1, 0.2 mmol/Kg
gadolinium at 5 cc/s) obtained 18 months
following resection of an anaplastic
oligoastrocytoma shows an enhancing
abnormality posterior to the deep margin
of the resection cavity. B) FDG-PET shows
subtle foci of increased glucose
metabolism corresponding to the foci of
enhancement, greater than the adjacent
white matter but less than adjacent grey
matter. This was felt to represent tumor
recurrence by the interpreting PET
specialist. C) Corrected CBV revealed
reduced blood volume within the lesion
(arrow), consistent with radiation necrosis
(perfusion raw data obtained at TR 500,
TE 65, 5-mm thick, 6-mm skip, 0.2
mmol/Kg gadolinium at 5 cc/s). Resection
of the abnormality confirmed radiation
effect without evidence of tumor.

28. 49-year-old patient with high-grade glioma who
underwent combined 3-T MR perfusion protocol.
A, Contrast-enhanced gradient-recalled echo T1-
weighted image shows cystic rim-enhancing
lesion with solid frontal parts.
B and C, In accordance with the Standardization
of Acquisition and Post-Processing study,
combined protocol of dynamic contrast-enhanced
(DCE) MR perfusion (transfer constant map, B)
was obtained first with 0.05 mmol/kg gadobutrol
at 2 mL/s and 20 mL saline flush followed by
dynamic susceptibility contrast-enhanced (DSC)
MR perfusion imaging (relative cerebral blood
volume map, C) with 0.05 mmol/kg gadobutrol
at 5 mL/s and 20 mL saline flush.
D, Although small amount of contrast medium
was used, signal intensity–time curve for DCE MR
perfusion shows excellent contrast enhancement,
resulting in high-quality perfusion maps.
E, Concentration-time curve for DSC MR
perfusion shows short and sufficient bolus
geometry and was not influenced by preload of
contrast medium.

29. Left temporal grade 3 glioma
imaged in accordance with
Standardization of Acquisition
and Post-Processing study
protocol.
A–E, Nonenhancing part of lesion
(A and B) shows mild increase in
plasma volume (vp) image (C).
Transfer constant (ktrans) (D) shows
no abnormality whereas relative
cerebral blood volume image (E)
clearly shows high value as
marker of anaplastic
transformation.

30. PMR TIC (lower right) and rCBV
map (left) demonstrate very
high microvascular blood
volume. The low return to
baseline of the lesion TIC (green
curve) compared with normal
brain (purple curve) is
characteristic of high first-pass
leak in an extra-axial lesion
without a BBB. In this case, the
high permeability also produces
prominent enhancement on the
delayed post-Gd T1-weighted
image (upper right) in a pattern
strongly suggestive of
meningioma, but the distinctive
PMR findings illustrated can be
very helpful in the differential
diagnosis of less classical
appearing lesions.

31. Comparison of rCBV color map
(upper right) and TIC (lower
right) in regions of interest
selected within the dural-based
enhancing lesion (lower left,
purple) and an appropriate
region of interest in the
contralateral white matter
(lower left, green) demonstrate
the characteristic high first-pass
leak of a nonglial tumor (TIC)
and blood volume only
minimally higher than white
matter (TIC and rCBV color map).
In combination with the
appearance on coronal post-Gd
T1-weighted image (upper left),
the perfusion imaging strongly
suggests dural metastasis,
confirmed at biopsy to be from
non–small cell lung carcinoma.

32. Endothelial transfer constant (KPS) color map (left) and TICs pre and post normalization
(upper middle and upper right, respectively) demonstrate only minimally increased
permeability within the new ring-enhancing lesion (lower middle) in this patient post resection,
radiation, and chemotherapy for gliosarcoma. The relatively mild increase in permeability
suggested radiation necrosis rather than recurrence, as confirmed by the 6-month follow-up
postgadolinium T1-weighted image (lower right) showing no interval progression.

33. Magnetic resonance spectroscopy (MRS)
is proposed in addition to magnetic resonance imaging
(MRI) to help in the characterization of brain tumours by
detecting metabolic alterations that may be indicative of
the tumour class. MRS can be routinely performed on
clinical magnets, within a reasonable acquisition time and
if performed under adequate conditions, MRS is
reproducible and thus can be used for longitudinal
follow-up of treatment.
MRS can also be performed in clinical practice to guide the
neurosurgeon into the most aggressive part of the lesions
or to avoid unnecessary surgery, which may furthermore
decrease the risk of surgical morbidity.

34. Magnetic Resonance Spectroscopy (MRS)
is now a days considered as a main MRI investigation
modality in the clinical routine jointly with conventional
anatomical and functional magnetic resonance imaging
for studying brain tumours. MRS provides
complementary information about cellular metabolism.
This allows differentiating the brain tumours from
abscess, the diagnosis of the tumour type,
characterization of brain tumours, as well as local study of
the morphological abnormalities observed in conventional
MRI. The MRS could be used in the therapeutic follow-up
for evaluating the pathological active area of brain, and
allows optimizing the guided biopsy as well as to
differentiating recurrent tumour from a necrosis.

35. MR spectroscopy (MRS) relies on detection of metabolites within
tumor tissue. Although useful in the differential diagnosis of brain
tumors, MRS often can be nonspecific and suffers from low spatial
resolution. MRS may be more accurate, however, than MR perfusion
or conventional MRI for determining tumor margins. MR spectroscopy
is very valuable in the diagnosis and grading of brain tumors.
 Proton MRS is able to detect the following metabolites:
 N-Acetyl Aspartate (NAA) at 2 ppm: Marker of neuronal
density and viability
 Creatine (Cr) at 3 ppm: Energy metabolism, generation of
ATP
 Choline (Cho) at 3.2 ppm: Pathological alterations in
membrane turnover, increased in tumors
 Lipids (Lip) between 0.8 – 1.5 ppm: Breakdown of tissue,
elevated in brain tumors - lipids indicate necrosis

36. Lactate (Lac) at 1.3 ppm, inverted at 144ms: produced by an
anaerobic metabolism, found in tumor containing zones of necrosis

38. A 50-year-old male with non-tumorous condition (inflammation) was misdiagnosed as
tumor due to non-specific MRS pattern. A and B, ill defined enhancing lesion is noted in
the left temporal lobe with extensive brain edema (A: T2-weighted image, B:
postcontrast T1-weighted image). C and D, MR spectroscopy of the mass shows slightly
increased choline and lactate with decreased NAA, interpetating as tumor. Lactate
inversion at long TE is needed for correct diagnosis.

39. 5 years ago, tumor removal state of astrocytoma in the R para sagittal region.
A 49-year-old female with non-tumorous condition (gliosis with focal calcification) was
misdiagnosed as tumor due to non-specific MRS pattern. A and B, T2 high signal intensity
mass is noted in the right rolandic region with suspicious subtle enhancement (A: T2-
weighted image, B: postcontrast T1-weighted image). C and D, MR spectroscopy of the
mass shows increased choline and lactate with decreased NAA, interpretating as residual
or recurrent tumor. Choline level and choline/NAA ratio are needed for correct diagnosis.

40. A 52-year-old male with high grade tumor (glioblastoma, WHO grade IV) was
misdiagnosed as low grade tumor due to nonspecific MRS pattern and too small number
of VOIs. A and B, T2 high signal intensity lesion is noted in the right hippocampus and
anterior temporal lobe without definite contrast enhancement (A: T2-weighted image,
B: postcontrast T1-weighted image). C and D, MR spectroscopy of the mass shows slightly
increased choline, interpretating as low grade tumor.

41. A 7-year-old female with low grade tumor (pilocytic astrocytoma, WHO grade
I) was misdiagnosed as high grade tumor due to peculiar tumor histopathology of
pilocytic astrocytoma. A, B and C, Lobulated T2 high signal intensity mass is noted
in the suprasellar and intrasellar region with well enhancement and scattered
microcystic portion (A and B: T2-weighted image, C: postcontrast T1-weighted
image). D and E, MR spectroscopy of the mass shows markedly increased choline
and lactate with decreased NAA, interpretating as high grade tumor.

42. A 26-year-old male with low grade tumor (oligodendroglioma, WHO grade
II) was misdiagnosed as high grade tumor due to peculiar tumor histopathology of
oligodendroglioma. A, B and C, Focal cystic encephalomalacic change is noted in the
right frontal lobe with peripheral enhancing portion (A: T2-weighted image, B: FLAIR
image, C: postcontrast T1-weighted image). D and E, MR spectroscopy of the lesion
shows markedly increased choline and lactate with decreased NAA, interpretating as
high grade tumor.

43. A 44-year-old female with low grade tumor (meningioma, WHO grade I) was
misdiagnosed as high grade tumor due to nonspecific MRS pattern. A and B, T2
isosignal intensity lesion is noted in the L cerebellar region. This lesion show well
enhancement with internal cystic portion (A: T2-weighted image, B: postcontrast T1-
weighted image). C and D, MR spectroscopy of the lesion shows markedly increased
choline and lactate with decreased NAA, interpretating as high grade tumor.

44. A 48-year-old male with low grade tumor (fibrillary astrocytoma, WHO grade II)
was misdiagnosed as high grade tumor due to nonspecific MRS pattern. A and B,
Subtle enhancing mass with cystic portion is noted in the right rolandic region (A:
T2-weighted image, B: postcontrast T1-weighted image). C and D, MR spectroscopy
of the lesion shows increased choline and lactate, interpretating as high grade tumor.

46. A 31-year-old man with tumor (anaplastic oligoastrocytoma, WHO grade III) was
misdiagnosed as non-tumorous condition (necrosis) due to mislocated VOI at necrotic
portion. A and B, Contrast enhancing mass lesion is noted in the right temporal lobe
(A: FLAIR image, B: postcontrast T1-weighted image). C and D, MR spectroscopy of
the mass shows marked elevation of lactate/lipid and decreased NAA without
significant increase of choline, interpretating as necrosis.

49. Patient with glioblastoma with oligodendroglioma component, WHO grade IV of IV.
(A) MRS spectrum from region of brain not affected by the tumor. (B) Spectrum from
a voxel within the tumor, showing elevated choline. (C) T1 MR image and (D) color-rendered
MRS image showing variations in the levels of choline within the tumor.

56. Sequential changes in spectra for a patient with a recurrent grade 4 glioma, which
was treated with gamma knife radiosurgery to the enhancing volume. The
examinations were obtained before treatment, 2 and 3 months after treatment. In
this case, there were numerous voxels outside the target that had abnormal
metabolism. Note the reduction of choline in the treated voxels but stable or
slightly increasing choline outside the target volume. Although the enhancing
volume dose increased after therapy, it is still smaller than the metabolic lesion.

57. Arrays of spectra from grade 2 (left), grade 3 (middle), and grade 4
(right) gliomas. Note the heterogeneity of the spectral patterns in these
lesions. Spectra that have metabolic abnormalities are shaded, and
those with peaks corresponding to lactate or lipid are marked with a “∗”.

58. Conclusions:
MR perfusion is an exciting imaging tool that allows assessment of
both tumor anatomy and physiology in one setting. Multiple studies have
shown that preoperative grading of brain tumors is not only possible using
MR perfusion methods, but is more accurate than that using conventional
MRI scanning alone. This can, in turn, be used to guide the surgeon to
perform biopsy on the most aggressive portions of a tumor. In the future,
it is also possible that MR perfusion could be used to more accurately
delineate tumor margins, in order to better plan resection and radiation
treatment of brain neoplasms. MR perfusion imaging, most notably the
delayed T1-weighted permeability methods, may also be valuable in
distinguishing radiation necrosis from tumor recurrence, thus sparing
patients from unnecessary treatment. Finally, MR perfusion methods, as a
surrogate marker for treatment outcome, are likely to play a central role in
the development of new antiangiogenic compounds. As advances in MR
technology take place, the role of MR perfusion in the care of neuro-oncologic
patients is likely to increase, and may eventually permit reliable,
noninvasive assessment of a patient’s prognosis and response to therapy.

59. The MR spectroscopy has a great interest in
the exploration and therapeutic strategies
of brain tumors. It allows a better general
combination and confrontation of functional
metabolism and morphological studies. The
technical development including multi-canals
bird cage coils technology, stronger magnetic
field gradients, and appropriate post-processing
software should allow advanced
and better involvement of MR spectroscopy
in brain cancer studies.

60. Thank You.