How-I-do-it

Brain Perfusion; How & Why

Nader Binesh, Ph.D.1; Marcel M. Maya, M.D.1; Helmuth Schultze-Haakh, Ph.D.2; Franklin G. Moser, M.D.1
1
Department of Imaging, Cedars Sinai Medical Center, Los Angeles, CA, USA
2
Siemens Medical Solutions, Cypress, CA, USA

Introduction
Cerebral perfusion is defined as the tissue per minute. In perfusion MR mean transit time - MTT) that can
steady-state delivery of nutrients and imaging, however, the term ‘perfusion’ be derived from the acquired data. In
oxygen via blood to brain tissue paren- comprises several tissue hemodynamic the evaluation of intracranial mass
chyma per unit volume and is typically parameters (cerebral blood volume – lesions, however, CBV appears to be
measured in milliliters per 100 g of CBV, cerebral blood flow – CBF, and the most useful parameter.

1 1

1 Slice positioning for the perfusion series (copied to the position of DarkFluid T2).

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Perfusion MR imaging methods take ising imaging tool rather than a standard years and have scanned, post-processed
advantage of signal changes that accom- proven technique for tumor grading and and dictated more than 1000 cases.
pany the passage of tracer (most com- staging. In the future, perfusion MR Here we would like to present our method
monly gadolinium based MR contrast imaging may become useful in the mon- of scanning and post-processing with
agents) through the cerebrovascular sys- itoring of treatment, and its results may a few clinical examples to highlight the
tem. Perfusion imaging can be performed also potentially serve as an arbiter when importance of perfusion in the diagnosis
with techniques based on dynamic sus- determining the efficacy of novel thera- of the lesion in question.
ceptibility contrast (DSC) or based on peutic agents, especially antiangiogenic
vascular permeability. DSC imaging allows therapy. Methodology
approximately 10 MR sections every sec- The DSC-MRI measurements can help Scanning
ond and is ideal for rapid dynamic imag- investigate hemodynamic abnormalities All the brain perfusion studies have been
ing. As the gadolinium contrast enters associated with inflammation, lesion acquired on Siemens MRI scanners and
the circulation, it induces susceptibility reactivity and vascular compromises. have been post-processed on a Siemens
changes by way of its paramagnetic Even a non-enhancing lesion may show Multi-Modality Work Place (MMWP),
properties; this in turn results in shorter high perfusion which suggests inflam- with Siemens perfusion evaluation soft-
T2* values and significant signal loss. matory reactivity that cannot be seen on ware. The scanners used were:
Curves showing intensity changes based conventional MRI. MAGNETOM Symphony with Quantum
on the concentration of gadolinium over Although brain perfusion has been gradients (software version syngo MR
time can be generated. The concentra- around for while [2] and its uses and A25 and syngo MR A30),
tion of gadolinium is a direct representa- advantages known for more than a MAGNETOM Symphony a Tim System
tion of the capillary density. From this, decade [2–4], it is not yet widely per- (syngo MR B15 and syngo MR B17),
the relative cerebral blood volume (rCBV) formed. This could be due to the follow- MAGNETOM Sonata (syngo MR A25),
can be determined, which corresponds ing reasons: MAGNETOM Avanto (syngo MR B15 and
to the volume of blood within brain tis- 1. The interpretation/quantification syngo MR B17), all 1.5T
sue. rCBV mirrors the neovascularization is not well established (or accepted) and the 3T MAGNETOM Verio (syngo MR
associated with tumor angiogenesis; in among radiologists. B15 and syngo MR B17).
adults with glial tumors, angiogenesis is 2. The post-processing of the images The perfusion was done as part of the
highly correlated to tumor grade, and is not yet automated and still needs routine (with contrast) brain examination
the rCBV of most high-grade glial tumors someone with expertise to perform for patients who were scheduled for sur-
is greater than that of low grade tumors. all or part of the post-processing. gery or at the request of a radiologist.
Perfusion MR imaging is increasingly 3. The technologists and radiologists Our routine brain exam consists of sagit-
being used as a diagnostic and research assume that it is hard to integrate into tal T1 (TSE), axial T2 (TSE), axial FLAIR
tool that provides maps of the regional the usual protocol. (TSE), axial EPI diffusion and post-con-
variations in cerebral microvasculature trast axial MPRAGE T1. The perfusion
of normal and diseased brains. With rel- Brain perfusion can easily be integrated series uses the sequence ep2d_perf that
atively short imaging and data process- into any brain imaging routine with can be found in the Siemens protocol
ing times and the use of a standard dose contrast. Instead of hand injection the tree under head-Advance-Diffusion & Per-
of contrast agent, perfusion MR imaging contrast bolus should be delivered by fusion. We modified the Siemens stan-
is a promising tool that can easily be a power injector. However, it is at the dard protocol slightly to suite the rest of
incorporated as part of the routine clini- discretion of the physician to apply con- our protocols to match primarily the
cal evaluation of intracranial mass lesions. trast media if need be. The perfusion slice thickness, slice gap and field-of-view
Although still investigational, MR imag- does not add any extra risk to a normal (FOV).
ing CBV measurements can be used as brain MRI examination, as in all these
an adjunct to conventional imaging to cases the patient would have been given The following are the steps to perform
help assess the degree of neovascular- a contrast agent anyway. The perfusion a brain perfusion study on a Siemens MR
ization in brain tumors, evaluate tumor data is acquired during the injection scanner:
grading and malignancy, identify tumor- without increasing the amount of Gado- ■ Make sure the patient has a good
mimicking lesions (such as radiation linium contrast. The addition of the intra-venous line (IV) with a needle
necrosis, cerebral abscess, and tumefac- perfusion adds about 2 minutes to the gauge of 18 or 20. Use the antecubital
tive demyelinating lesion (TDL)) by dem- examination time. Easy post-processing veins and avoid more peripheral
onstrating their lack of angiogenesis, may add informative maps aiding the placement of the needle.
and assess the status of viable tissue radiologists in their diagnoses of various ■ Hook the patient’s IV to an injector
surrounding an acute infarct. It must be brain lesions. and set the injection rate to 4 ml per
emphasized, however, that perfusion We have worked on brain perfusion second. A normal contrast dose of
MR imaging is a relatively new and prom- in our clinical setting for the past three 0.1 mM/kg should be used.

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■ Make sure the IV is good and shows 2

no resistance to flow.
■ Start the routine exam, and insert the
perfusion procedure just before the
post-contrast T1.
■ The perfusion imaging slices should
have the same positioning, thickness
and gap as the axial FLAIR or T2
sequences to facilitate a direct com-
parison of the perfusion results with
other pre- and post-contrast images
(Fig. 1).
■ Make sure that both the lesion and
cortical white matter are covered.
■ The phase encoding direction needs to
be anterior-posterior (A/P) to reduce
susceptibility artifacts.
After the pre-contrast portion of the
brain exam is done, be ready with the
injection: start the scan and inject the
contrast at the 8th measurement. The
scan has 50 time points (measurements)
of ~2 s each resulting in total time just
below 2 min. 2 Opening page of the perfusion application. The perfusion series has been dropped and
Send the main series to the workstation can be seen in the first quadrant (top left).
where you want to do the post-process-
ing of the images.

Post-Processing 3
■ On the Siemens workstation (MMWP
or Leonardo), open the perfusion
application (Application-Perfusion).
■ Open the Patient Browser and load the
main perfusion series into the Perfu-
sion Page (Fig. 2).
■ Click on the images and page through
to get to the slice where you can see
the area of interest (tumors etc.).
■ Identify an artery on the same slice.
■ Click on the small AIF icon:
A square appears on the image.
Place the square on the artery
(Fig. 3).
■ On the right side of the screen (Fig. 3),
select AIF, by choosing the best time
graphs, the ones with significant signal
drop (highlighted squares). Do so for
4 or more time-points, hold the Contr.-
key while clicking with the left mouse-
button.

3 The arterial input function (AIF) square is shown on a slice of the perfusion image data,
with the resulting 9x9 pixels time points on the right side. The highlighted region-of-inter-
est (ROI) is used to calculate the AIF from.

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4 ■ When done, click on the second tab:

Step 2: Set Time Ranges (Fig. 4). Move
the three time-lines, so that the first
one is at the start of the baseline, the
second one at the beginning of the
drop (Gad entry) and the third one at
the peak of the recovery, as shown
in Figure 4. Then click the check box
‘Confirm Time Ranges’.
■ Make sure the selector at the lower-
right side of screen is on ‘All Maps’.
■ Click on the color calculator/brain icon
at the bottom-right corner of the
screen. If the icon is dimmed
(grayed out) the time selection has not
been done yet. The calculation takes
about 20 – 30 seconds.

4 The resulted AIF, with the three time points properly shown. The first one is at the baseline,
second at the start of the drop and the third at the end of the drop (peak of recovery).

5A Once the calculation is done, the rCBV

(relative cerebral blood volume) and
rCBF (relative cerebral blood flow) color
images are displayed in the 4th quadrant,
of the screen, as shown in figure 5
(A and B). Toggle between series using
the ‘4’ and ‘5’ keys on the numerical key
pad (on right of keyboard). The third
quadrant shows the MTT (mean transit
time) and TTP (time-to-peak) maps. We
don’t bother with these.

5A Figure shows the perfusion screen, after the calculation is done. (5A) The rCBF is
displayed in the fourth quadrant (lower right) and the TTP is displayed in 3rd quadrant
(lower left).

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■ In the 4th quadrant, i.e. the bottom 5B

right segment, select series (right
mouse button), adjust the windowing
(center mouse button) and save as
new series (from the top menu, File-
Save As… (e.g. call them CBV_color or
CBF_color depending on which one
was selected).
These are just the color maps but the
pixel values are arbitrary.

Normalization of pixel values

To normalize the values:
■ Go to the Viewing card (right side
tabs) and open the series ‘CBV_color’.
■ Scroll to the top of the brain where
you can see the cortical white matter
without any distortions.

5B The rCBV is displayed in the fourth quadrant (lower right) and the MTT is displayed in 3rd
quadrant (lower left).

6
■ Using the free hand drawing (right
side panel), draw an enclosure (Fig. 6),
which only contains healthy white
matter, one on each side, if possible,
and on two slices, if possible.
■ Read the mean signal values and cal-
culate their average (avg) mean value
(adding all the values and divide by
the number of samples used).
■ Select the whole series (right mouse
button). From the top menu choose
‘Evaluation- Dynamic Analysis –
Divide…’.

6 Typical region selection for the cortical white matter tissue, to find the average
healthy white matter intensity.

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7 ■ In the new window (Fig. 7) enter

the mean value (avg from above) as
the constant and rename the final
series to CBV_normalized_avg
under ‘Result Series Description’.
Press ok.
■ Open the browser and select the
‘CBV_color’ series.
■ From the Application tab, choose:
MR – DICOM – Save as RGB. This
creates a series automatically
named ‘CBV_color_RGB’, adding ‘_
RGB’ to the original series name.
This makes the CBV_color series
RGB-color coded so that it can be
seen in color on PACS workstations.
■ Do the same for ‘CBF_color’.

7 The dialog box which opens for dividing the whole rCBV by a number
(average Cortical WM).

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Discussion
Following the above procedure we have have CBV values normalized to white matter (normalized value). In the litera-
done many brain perfusion studies and matter. By simultaneously displaying and ture describing a few studies with an
have used them to grade tumors. The correlating the color CBV images with aggressive tumor the perfusion ratio (with
idea of having the color maps and the the normalized ones, the radiologist is respect to white matter) was above 2.5
normalized version is that the normalized able to see the tissues color coded and [5]. By using this method a radiologist
version appears only in gray scale on can read the corresponding perfusion can evaluate and grade a tumor more
PACS stations, but its pixel intensities values with respect to healthy white quantitatively.

Case reports
To illustrate the usefulness of perfusion imaging in clinical practice,
here are four clinical examples from our practice:

Case 1
A 64-year-old female with a history showed no enhancement. This pointed sion images (rCBV) (Fig. 8C) showed
of brain tumor received radiation and to a low grade tumor. A follow-up MRI highly perfused tissues pointing to
chemotherapy treatment a few months with perfusion was performed, which a high grade neoplasm, which was
prior to our examination. The initial again showed abnormal hyperintensity subsequently resected. Histology
MRI showed abnormal signal on FLAIR on FLAIR (Fig. 8A) and no gadolinium confirmed high grade astrocytoma.
(IR T2), but the T1w post-contrast enhancement (Fig. 8B), but the perfu-

8A 8B 8C

8A Axial FLAIR 8B Axial post T1 8C Perfusion map CBV

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Case 2
A 60-year-old female with history 9A 9B

of metastatic lung cancer, presented

with metastatic nodule in the left
occipital lobe. She underwent crani-
otomy followed by postoperative
radiotherapy to the surgical bed. The
one year follow-up brain MRI showed
minimal enhancement on post-con-
trast MRI. The two year follow-up
showed a nodular mass, which further
grew on short term follow-up. The
diagnosis could be either new tumor
growth or radiation necrosis. The low
signal of rCBV in her perfusion exam-
ination pointed toward radiation
necrosis rather than tumor re-growth.
The enhancing part was subsequently
excised and pathology confirmed
radiation necrosis.

9A Axial post T1 (pre-surgical) 9B Axial post T1 (one year post surgery)

9C 9D 9E

9C Axial post T1 (two years post surgery) 9D Axial post T1 9E Axial perfusion map CBV
(2 years and 2 months post surgery) (2 years and 2 months post surgery)

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Case 3
The routine MRI of a 48-year-old right- tricular white matter, which had fea- choline signal. The perfusion protocol
handed man showed a lesion at the tures suggestive of tumoractive was performed and both the rCBV and
right thalamus suspected of low grade multiple sclerosis (MS), but the possi- rCBF showed low values (close to those
glioma. Subsequent imaging showed bility of primary brain neoplasm could of normal white matter). That pointed
a lesion involving the right posterolat- not be excluded, especially as the MR to MS with a low possibility of an addi-
eral thalamus posterior to the periven- spectroscopy (MRS) showed elevated tional primary brain neoplasm.

10A 10B 10C

10A Axial FLAIR 10B Axial post T1 10C Single Voxel Spectroscopy

10D 10E 10F

10D Axial perfusion map CBV 10E Follow-up axial FLAIR 10F Follow-up axial post T1

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Case 4
A 31-year-old HIV-positive male with 11A 11B
history of head trauma, and drug
abuse, was admitted to emergency
with chief complaint of right side
weakness and confusion. The initial CT
exam of the brain indicated findings
consistent with multiple, predomi-
nantly cortically based infarcts in the
bilateral frontal and temporal lobes.
No hemorrhage was seen. The follow-
ing MRI showed multiple areas of
abnormal T2 signal. The diffusion
images showed T2 shine through effect.
There was no significant mass effect
from these lesions. The findings were
suggestive of a diagnosis of acute dis-
seminating encephalomyelitis or tume-
factive MS. No sign of hemorrhage 11A Axial FLAIR 11B Axial diffusion-weighted imaging (b=1000)
was observed. On the CBV images
obtained from perfusion, the abnor- 11C 11D

mal areas appeared dark, indicating

low perfusion. In view of the immuno-
suppressed condition of the patient,
craniotomy and biopsy was performed
to exclude opportunistic infections
and neoplasms. Surgical pathology
confirmed the diagnosis of acute dis-
seminating encephalomyelitis. Follow-
up MRI demonstrated slight regression
of the lesions.

11C Axial post T1 11D Perfusion map CBV

References
1 L. Ostergaard. “Principles of Cerebral Perfusion 5 E.A.Knopp et al. Glial Neoplasms: “Dynamic
Imaging by Bolus Tracking” J Mag Reson Imaging Contrast-enhanced T2*-weighted MR Imaging” Contact
22 (2005) 710. Radiology 211 (1999) 791. Nader Binesh, Ph.D.
2 C.L. Partain. “Brain Perfusion Imaging Using 6 Cha S, Pierce S, Knopp EA, et al. Dynamic con- MR Physicist
Magnetic Resonance”. Editorial J Mag Reson trast-enhanced T2*-weighted MR imaging of Cedars-Sinai Medical Center
Imaging, 22 (2005) 691. tumefactive demyelinating lesions. AJNR Am J 8700 Beverly Boulevard
3 Soonmee Cha. “Perfusion MR Imaging of Brain Neuroradiol 2001; 22:1109 –1116. Los Angeles, California 90048
Tumors” Top Magn Reson Imaging 15 (2004) 279. USA
4 Rosen BR, et al. “Susceptibility contrast imaging Phone: +1 310 423 4056
of cerebral blood volume: Human experience” [email protected]
Magn Reson Med 22 (1991) 293.

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