Post on 02-May-2023
Original Investigation
Assessment of Splenic Perfusion inPatients with Malignant Hematologic
Diseases and Spleen Involvement,Liver Cirrhosis and Controls Using
Volume Perfusion CT (VPCT):
A Pilot Study
Alexander W. Sauter, MD, Stefan Feldmann, MDent, Daniel Spira, MD, Maximilian Schulze, MD,Ernst Klotz, PhD, Wichard Vogel, MD, Claus D. Claussen, MD, Marius S. Horger, MD
Ac
FrD.HeSeFo13sp
ªdo
Rationale and Objectives: The aim of this study was to assess splenic perfusion in patients with spleen involvement in malignanthematologic diseases and liver cirrhosis and in controls without hepatosplenic disease using volume perfusion computed tomography.
Materials and Methods: Between October 2009 and December 2011, 14 hematologic patients with known spleen involvement were
recruited. An additional 17 consecutive patients without known splenic or liver disease were enrolled as controls, as well as 29 patientswith liver cirrhosis and portal hypertension. A 40-second volume perfusion computed tomographic scan of the upper abdomen was
performed. Analysis included measurement of splenic volume, blood flow (BF), blood volume (BV), Ktrans, and mean transit time (MTT).
Results: In lymphoma patients, mean splenic volume and perfusion parameters were as follows: splenic volume, 1125.34 mL; BF,61.24 mL/100 mL/min; BV, 16.53 mL/100 mL; Ktrans, 37.00 mL/100 mL/min; and MTT, 12.42 seconds. All perfusion values of patients
with lymphoma and cirrhosis differed significantly, except for BV, compared to controls. For patients with lymphoma, significant correla-
tions were found between splenic volume and BF (r =�0.683, P = .000), splenic volume and BV (r =�0.525, P = .002), and splenic volume
andMTT (r = 0.543,P = .001). During treatment, significant correlations between the diameters of nodular lymphoma target lesions, splenicvolume, and the perfusion parameters were present for splenic volume (r = 0.601, P = .002), BF (r = �0.777, P = .000) and BV (r = �0.500,
P = .011).
Conclusions: Volume perfusion computed tomography represents a novel tool for the assessment of splenic perfusion. Preliminaryresults in patients with spleen involvement reveal lower perfusion values compared to controls or patients with cirrhosis. Therefore, this
technique might provide additional information in clinical routine.
Key Words: CT perfusion; volume-perfusion computed tomography; spleen; lymphoma; liver cirrhosis.
ªAUR, 2012
As a result of rare primary splenic diseases (1), the spleen
is often considered ‘‘silent and forgotten’’ (2). On the
other hand, secondary manifestations of hematologic,
immunologic, oncologic, infectious, vascular, and systemic
disorders are frequently found in the spleen (2). Forty-four
ad Radiol 2012; -:1–9
om the Department of Diagnostic and Interventional Radiology (A.W.S., S.F.,S., M.S., C.D.C., M.S.H.) and the Medical Center, Department ofmatology and Oncology (W.V.), University Hospital of T€ubingen, Hoppe-yler-Straße 3, D-72076 T€ubingen, Germany; and Siemens Healthcare,rchheim, Germany (E.K.). Received September 2, 2011; accepted January, 2012. This study was supported by Siemens Healthcare. Address corre-ondence to: A.W.S. e-mail: alexander.sauter@klinikum.uni-tuebingen.de
AUR, 2012i:10.1016/j.acra.2012.01.007
percent of patients with lymphoma have splenic involvement
(3). Splenomegaly is a common but unspecific finding, as
enlarged spleens do not necessarily indicate lymphoma infil-
tration (4), and only 1% to 2% of all patients with non-
Hodgkin’s lymphoma present with such splenic enlargement
(5). Spleen involvement is common in mantle cell lymphoma
and follicular lymphoma (5,6), as well as chronic lymphatic
leukemia (7–9). Accurate staging with assessment of splenic
disease is essential for clinical management and follow-up
(10). However, a study by Munker et al (11) revealed a low
accuracy of only 15% to 37% for computed tomography
(CT) and a disappointing correlation with histologic state.
Nevertheless, CT is the most frequently used stagingmodality.
Especially for diffuse involvements, positron emission
1
SAUTER ET AL Academic Radiology, Vol -, No -, - 2012
tomography (PET) using [18F]-fluorodeoxyglucose (FDG)
seems to be superior to CT (12). Secondary portal hyperten-
sion due to either direct lymphoma infiltration of the liver (13)
or mediastinal compression of the superior vena cava (14) may
additionally alter splenic perfusion. In a similar scenario, portal
hypertension in liver cirrhosis can prolong blood transit time
because of splenic venous congestion and decreased splenic
perfusion (15). Various imaging techniques such as isotope
scintigraphy (16–18) and [15O]-labeled water PET (19) have
been applied for the assessment of hepatic and splenic perfu-
sion. These techniques are complex and are available only
at specialized imaging sites. Functional CT, based on the
exchange of iodinated contrast material between the intravas-
cular space and the extravascular interstitial space, is an inter-
esting approach that can be integrated in the clinical routine
with manageable effort (20). This method evolved from
single-location dynamic sequences (15,21,22) toward multi–
detector row computed tomographic perfusion (23). Recently,
Goetti et al (24) applied four-dimensional spiral-mode for
computed tomographic liver perfusion with 128-row CT and
coverage of up to 14.8 cm.
The aim of our study was to assess and compare the ranges
of splenic perfusion using this new method. In the first step,
a group of hematologic patients with spleen involvement
was analyzed. Elderly patients in particular require special
attention, because in this group, liver cirrhosis is frequently
(23.7%) undiagnosed (25). Therefore, we additionally
analyzed splenic perfusion in a population with proven liver
cirrhosis, portal hypertension and hepatocellular carcinoma
(HCC) who had undergone liver perfusion CT prior to trans-
arterial chemoembolization. Finally, a group of patients who
had undergone tumor perfusion CT for other purposes but
presented with neither splenic diseases nor portal hyperten-
sion were included as normal controls.
To our knowledge, this is the first report in the literature
dealing with the role of volume perfusion CT (VPCT) for
the assessment of splenic perfusion differences in patients
with lymphomatous spleen involvement, patients with
cirrhosis, and controls.
MATERIALS AND METHODS
Study Population
Patients aged $30 years were enrolled consecutively from
October 2009 through December 2011 and analyzed retro-
spectively. Data were prospectively acquired in previous
perfusion studies approved by the local ethics committee,
including therapy monitoring in patients with lymphoma,
HCC, and general cancer disease with palliative care. Exclu-
sion criteria for contrast application included kidney dysfunc-
tion (defined as a serum creatinine level > 150 mmol/L),
known hypersensitivity to iodine-containing contrast media,
pregnancy, and untreated hyperthyroidism. All patients
provided written informed consent, including information
about radiation exposure.
2
For the first group, 14 patients (four women, 10 men; mean
age, 61.7 � 8.3 years; range, 49.5–76.8 years) with hemato-
logic diseases (B-cell chronic lymphocytic leukemia, n = 3;
B-cell non-Hodgkin lymphoma, n = 3; diffuse large B-cell
lymphoma, n = 2; peripheral T-cell lymphoma not otherwise
specified, n = 3; mantle cell lymphoma, n = 2; splenic
marginal zone lymphoma, n = 1) with spleen involvement
were examined. These patients were assessed either for initial
diagnosis or for detection of progressive disease. Follow-up
perfusion measurements were performed in 9 patients.
Evaluation of the disease course was accomplished using
Cheson criteria considering all measurable lymphoma
manifestations.
The second group included 29 patients (four women,
25 men; mean age, 65.0 � 8.6 years; range, 46.0–78.0 years)
with liver cirrhosis and HCC. Twenty-two patients were
classified as Child-Turcotte-Pugh class A and seven patients
as class B. All patients had signs of liver cirrhosis and portal
hypertension on contrast-enhanced CT (irregular and
nodular surface, blunt edge, parenchymal abnormalities,
morphologic changes [atrophy of the right lobe, atrophy of
the medial segment, hypertrophy of the lateral segment,
hypertrophy of the caudate lobe, widened pericholecystic
space, enlarged periportal space], manifestations of portal
hypertension [splenomegaly, splenic vein dilatation, ascites,
gastric and esophageal varices, paraumbilical collaterals, sple-
norenal shunt, other sites of collaterals] [26]) and had under-
gone liver perfusion CT for evaluation prior to transarterial
chemoembolization. Patients with portal vein thrombosis
and transjugular intrahepatic portosystemic shunts were
excluded.
Finally, 17 patients (five women, 12 men; mean age, 59.7�14.4 years; range, 34.6–78.1 years) who had been examined
with perfusion CT because of tumor manifestation in the
upper abdomen without hepatic or splenic spread were
included. These patients had the following diagnoses:
non-small-cell lung cancer (n = 1), pancreatic cancer
(n = 4), cancer of unknown primary (n = 1), esophageal
cancer (n = 4), renal cell carcinoma (n = 1), leiomyosarcoma
(n = 2), gastric cancer (n = 1), colorectal cancer (n = 1),
nondysgerminoma (n = 1), and Echinococcus granulosus
(n = 1). In this group, patients with signs of liver cirrhosis
on contrast-enhanced CTwere excluded.
Computed Tomographic Protocol
All examinations were performed with a 128-row computed
tomographic scanner (Somatom Definition AS+; Siemens
Healthcare, Forchheim, Germany). First, non-enhanced
low-dose CT of the thorax and abdomen was performed.
Subsequently, an experienced radiologist analyzed the non-
enhanced low-dose computed tomographic findings, and
a scan range of 6.9 to 9.6 cm z-axis coverage centered to the
spleen hilum was planned, followed by VPCTusing an adap-
tive spiral scanning technique. The following scan parameters
were used: tube voltage, 80 kV; collimation, 128 � 0.6 mm;
Academic Radiology, Vol -, No -, - 2012 SPLENIC PERFUSION
and a total of 22 scans. Depending on the bodyweight, patients
were examinedwith tube current–time products of 80, 100, or
120 mAs. The total scanning time for VPCTwas 40 seconds.
During perfusion scanning, patients were asked to resume
shallow breathing for the entire duration of the study. A
volume of 50 mL Ultravist 370 (Bayer Vital, Leverkusen,
Germany) at a flow rate of 5 mL/s was injected in an
antecubital vein through an 18-gauge needle (Vasofix; B.
Braun Melsungen AG, Melsungen, Germany) followed by
a saline flush of 50 mL sodium chloride at 5 mL/s. Scanning
was started after a delay of 7 seconds. Contrast material was
administered using a dual-head pump injector (Medtron, Saar-
bruecken,Germany). After the perfusion scans, another 80mL
of contrast medium was injected, and chest, abdominal, and
neck computed tomographic scans for staging purposes were
subsequently performed. One set of axial images with a slice
thickness of 3 mm for perfusion analysis was reconstructed
without overlap, using a medium-smooth tissue convolution
kernel (B10f). All images were then anonymized and trans-
ferred to an external workstation (Multi-ModalityWorkplace;
Siemens Healthcare) for analysis.
Quantitative Perfusion Analysis
Data evaluation was performed using syngo Volume Perfusion
CT Body (Siemens Healthcare), on the basis of the Tofts
model. No clinical data except gender and age were provided
to the reader. Motion correction and noise reduction were
performed for all image sets using the algorithms integrated
in the perfusion postprocessing software. The algorithms
are based on non-rigid deformable registration for anatomic
alignment (27,28) and a dedicated noise reduction
technique for dynamic data (29).
A volume of interest was drawn manually around the entire
spleen on the maximum intensity projection image set. Care
was taken to exclude hilar blood vessels. Navigation
throughout all slices was performed to ensure a good selection
result. Air, fat, bone, and other dense structures were excluded
with a threshold-based segmentation. For the arterial input
function, a region of interest was placed inside the abdominal
aorta. Perfusion parameter volume maps of blood flow (BF),
blood volume (BV), Ktrans, and mean transit time (MTT)
were generated. Splenic volume was determined using syngo
Oncology (Siemens Healthcare) from portal venous–phase
enhanced abdominal scans.
Statistical Analyses
Descriptive statistics including means and standard deviations
of the splenic volumes and perfusion parameters were calcu-
lated using JMP version 8.0.2 (SAS Institute Inc, Cary,
NC). Differences between the perfusion parameters of the
groups were tested using unpaired t tests. Correlations were
analyzed using Spearman’s rank correlation coefficient (r).
Differences were considered to be significant for two-tailed
P values <.05.
RESULTS
All perfusion studies were completed successfully and could be
analyzed using the software.
The mean dose-length products for perfusion measurements
in the upper abdomen were 480.0 � 97.5 mGy $ cm for the
spleen involvement group, 398.0 � 234.5 mGy $ cm for the
cirrhotic group, and 369.4 � 93.6 mGy $ cm for the control
group.
Spleen Involvement
Results of perfusion measurements in patients with spleen
involvement by malignant hematologic diseases are summa-
rized in Table 1. Table 2 provides a detailed parameter
assembly for each patient. Splenic involvement could be
confirmed in two patients with FDG-PET (patients 2 and
10) and in one patient with histology after splenectomy
(patient 2).
Mean splenic volume and perfusions parameters (BF,
BV, Ktrans, and MTT) were as follows: splenic volume,
1125.34 � 784.24 mL; BF, 61.24 � 22.80 mL/100 mL/min;
BV, 16.53 � 14.32 mL/100 mL; Ktrans, 37.00 � 12.97 mL/
100 mL/min; and MTT, 12.42 � 2.66 seconds. Splenic
volume (P < .001), BF (P < .001), Ktrans (P = .011), and
MTT (P = .023) differed significantly from the control group,
whereas BV (P = .095) did not. Compared to cirrhotic
patients, only Ktrans (P < .001) revealed a significant differ-
ence, whereas splenic volume (P = .077), BF (P = .114),
BV (P = .618), and MTT (P = .071) did not. Significant
correlations were found between splenic volume and BF
(r = �0.683, P = .000), splenic volume and BV
(r = �0.525, P = .002), and splenic volume and MTT
(r = 0.543, P = .001) but not for splenic volume and Ktrans
(r = 0.071, P = .698). Areas of focal spleen involvement
were present in only six patients on the basis of hypodense
areas in the portal venous–phase enhanced abdominal scans.
In patient 8, the hypodense lesions disappeared under therapy.
Nine patients were followed up during ongoing treatment
(see Table 2). As expected, follow-up perfusion studies
revealed decreases in BF and BV in patients experiencing
progressive disease (patient 8, May to August 2010; and
patient 11), whereas in seven patients (patient 7; patient 8,
November 2010 to March 2011; and patients 9, 10, 12, 13,
and 14) undergoing treatment, increases of BF and BV
associated with a decrease in splenic volume were registered.
Additionally, the diameters of nodular lymphoma target
lesions were correlated with splenic volume and the perfusion
parameters of the spleen. Interestingly, significant correlation
were present for splenic volume (r = 0.601, P = .002), BF
(r = �0.777, P = .000), and BV (r = �0.500, P = .011)
but not for Ktrans (r = �0.286, P = .166) or MTT
(r = 0.341, P = .096).
Figure 1a shows the BF map of patient 2, with peripheral
T-cell lymphoma not otherwise specified. The black stars
indicate an area of low BF. This area corresponds to increased
3
TABLE 1. Splenic Volumes and Perfusion Parameters for All Groups
Variable
Malignant
Hematologic
Diseases P*
Control
Group Py
Entire
Cirrhotic
HCC Group
Cirrhotic
HCC Child
Class A Group
Cirrhotic
HCC Child
Class B Group
Splenic volume (mL) 1125.34 � 784.24 <.001 253.79 � 75.28 <.001 639.09 � 355.22 594.56 � 375.96 779.05 � 253.04
Blood flow (mL/100 mL/min) 61.24 � 22.80 <.001 95.66 � 25.25 .002 72.38 � 21.00 74.51 � 22.93 65.67 � 12.24
Blood volume (mL/100 mL) 16.53 � 14.32 .095 16.39 � 4.64 .089 13.91 � 6.46 13.39 � 6.58 15.54 � 6.27
Ktrans (mL/100 mL/min) 37.00 � 12.97 .011 49.12 � 15.58 .036 52.21 � 10.43 51.84 � 11.19 53.38 � 8.22
Mean transit time (seconds) 12.42 � 2.66 .023 10.67 � 2.05 <.001 13.77 � 3.57 13.56 � 3.91 14.46 � 2.32
HCC, hepatocellular carcinoma.
Data are expressed as mean � standard deviation.
*Patients with malignant hematologic diseases versus controls.yControls versus entire cirrhotic HCC group.
SAUTER ET AL Academic Radiology, Vol -, No -, - 2012
FDG uptake (Fig 1b). Figures 1c to 1e present the maps for
BV, Ktrans, and MTT. No clear and circumscribed areas are
seen in these maps. Fast and slow enhancing compartments
of the spleen cause the heterogeneous patterns. The patient
underwent splenectomy, and the enlarged spleen was histo-
logically analyzed. Figure 1f shows a hematoxylin and eosin
section of the spleen. A diffuse infiltration was present, but
also fine nodular infiltrates (surrounded by black stars) could
be seen. The disease was so advanced that even some trabec-
ular arteries were infiltrated by lymphoma cells (Fig 1g).
Patients with Nonhepatosplenic Disease and LiverCirrhosis
The splenic volumes and perfusion parameters for the
cirrhotic HCC groups and control groups are shown in
Table 1.
Not surprisingly, the mean splenic volume of the cirrhotic
HCC group (639.09 � 355.22 mL) was higher than that of
the control group (253.79 � 75.28 mL) (P < .001). The
mean BF in the cirrhotic HCC group was 72.38 mL/100
mL/min, compared to 95.66 mL/100 mL/min in control
patients (P = .002). The mean BVs of the two groups
(13.91 and 16.39 mL/100 mL) did not differ significantly
(P = .089), while the mean Ktrans values (52.21 and 49.12
mL/100 mL/min) were different (P = .036). Also, the
MTTs showed a significant difference (13.77 vs 10.67
seconds, P < .001). No significant correlations were found
between splenic volumes and the perfusion parameters in
the control patients (splenic volume and BF: r = 0.123,
P = .632; splenic volume and BV: r = �0.037, P = .883;
splenic volume and Ktrans: r = �0.002, P = .989; and splenic
volume and MTT: r = �0.052, P = .839) and the cirrhosis
patients (splenic volume and BF: r=�0.151, P= .432; splenic
volume and BV: r = 0.238, P = .211; splenic volume and
Ktrans: r = 0.080, P = .676; and splenic volume and MTT:
r = 0.174, P = .362).
The cirrhotic HCC group can be further subdivided into
patients in Child classes A and B (see Table 1). Splenic volumes
(Child class A, 594.56 � 375.96 mL; Child class B, 779.05 �253.04 mL; P= .088), BF values (Child class A, 74.51� 22.93
4
mL/100 mL/min; Child class B, 65.67� 12.24 mL/100 mL/
min; P = .341), BV values (Child class A, 13.39 � 6.58 mL/
100 mL; Child class B, 15.54 � 6.27 mL/100 mL; P = .372),
Ktrans values (Child class A, 51.84 � 11.19 mL/100 mL/min;
Child class B, 53.38 � 8.22 mL/100 mL/min; P = .899), and
MTTs (Child class A, 13.56 � 3.91 seconds; Child class B,
14.46 � 2.32 seconds; P = .252) did not differ significantly.
DISCUSSION
In this study, we aimed to determine the potential benefit of
VPCT for the assessment of normal and pathologic splenic
perfusion, including detection of abnormalities related to
cell infiltration in malignant hematologic diseases.
The spleen is a blood-filled organ playing important roles
with regard to red blood cells and the immune system. It
represents the largest filter of blood and is organized as
a tree of branching arterial vessels with the arterioles ending
in a venous sinusoidal system (30). Splenic architecture
comprises many communicating compartments that build
up two distinct tissues, the red and the white pulp. Red
pulp is composed of nonanastomosing arterial vessels, thin-
walled venous vessels called splenic sinuses, splenic cords lying
between the sinusoids, and draining red pulp veins; white pulp
consists of lymphatic tissue (31). The dynamics of splenic
microcirculatory BF and the role of the spleen with respect
to red blood cells have been elucidated by means of several
different experimental approaches. Different microscopic
approaches have provided complementary information and
have clarified a number of important issues. Hence, exploiting
the quantitative analysis of BF and other perfusion character-
istics for spleen characterization using available and relatively
low-cost technology has the potential to provide new insights
into this complex and neglected organ (32).
A major focus in daily hemato-oncologic diagnosis is the
accurate detection of splenic involvement with malignant
hematologic diseases. Noninvasive assessment of splenic
involvement in lymphoma is important for both staging and
therapeutic purposes. In Hodgkin’s disease, for instance, the
spleen is the abdominal location most commonly affected by
occult disease and in 10% of the cases is the only site of
TABLE 2. Patients with Malignant Hematologic Diseases and Spleen Involvement
Patient Age (y) Sex Diagnosis First Diagnosis Treatment Study Date Splenic Volume BF BV Ktrans MTT
Baseline
1 58.6 M Low-grade B-NHL 02.2007 No 10.2010 1826.31 59.35 6.51 52.46 14.29
2 72.7 M Relapse PTCL-NOS 03.2011 6 � CHOP (5/06 to 8/06) 01.2011 560.21 87.69 13.97 47.60 10.54
3 68.6 F SMZL 12.2010 No 03.2010 1878.34 55.82 7.45 43.36 15.13
4 65.7 M B-CLL 07.2005 15 � KNOSPE (5/07 to 12/07)
1 � rituximab (6/08)
5 � R-bendamustine (6/08 to 10/08)
5 � fludarabine/cyclophosphamide
(9/09 to 1/10)
04.2011 648.92 46.76 8.37 30.78 12.16
5 76.8 M B-CLL 01.1998 5 � KNOSPE (12/01 to 3/02)
6 � KNOSPE (7/03 to 10/03)
4 � R-bendamustine (10/09 to 2/10)
06.2010 2057.63 51.62 14.09 55.17 16.86
Baseline and follow-up
6 49.5 M B-CLL 10.2005 No 01.2011 503.45 64.88 13.20 22.09 10.11
6 � R-FC (3/11 to 8/11) 09.2011 320.55 117.95 55.67 202.42 11.97
7 63.6 F Relapse low-grade
B-NHL
08.2010 6 � VACOP-B (2/95)
6 � R-bendamustine (8/07 to 2/08) 01.2011
922.71 25.40 3.56 28.36 13.66
2 � R-VIPE (1/11) 02.2011 457.40 73.98 15.42 40.21 11.29
8 56.6 M Low-grade B-NHL 10.2008 6 � R-CHOP + 2 � rituximab
(10/08 to 3/09)
05.2010 1187.25 45.53 17.43 24.15 19.00
1 � R-VIPE (10/10) 08.2010 1748.80 37.51 4.93 36.07 16.01
2 � R-VIPE (11/10) 11.2010 1168.38 43.23 6.83 39.53 13.28
No 12.2010 1168.83 45.08 6.53 41.28 12.44
4 � R-bendamustine (11/10 to 6/11) 03.2011 1116.84 37.83 5.50 29.26 12.76
9 56.6 F DLBCL 07.2010 No 07.2010 1886.14 13.00 3.13 12.46 8.79
4 � R-CHOP (7/10 to 9/10) 09.2010 448.37 60.91 9.72 37.55 11.61
2 � R-CHOP + 2 � rituximab
(10/10 to 12/10)
01.2011 329.28 65.88 9.89 47.66 9.72
No 06.2011 320.18 94.16 41.47 33.84 10.90
10 67.7 M Relapse DLBCL 12.2010 6 � CHOP-21 (7/02 to 11/02) 02.2011 513.55 48.09 7.62 35.62 13.64
1 � R-VIPE (2/11) 03.2011 275.24 99.54 17.33 37.40 8.30
2 � R-VIPE (3/11) 04.2011 279.67 79.95 14.80 36.09 7.71
1 � HD + PBSCT (4/11) 08.2011 260.00 69.21 10.50 37.63 9.16
11 51.5 M PTCL-NOS 05.2010 2 � CHOP + 2 � VIPE (5/10 to 8/10) 08.2010 1856.29 49.86 15.43 47.25 14.30
HD + PBSCT (10/10) 12.2010 2982.11 32.37 4.20 36.13 12.12
12 50.5 F PTCL-NOS 02.2003 No 04.2010 1862.25 50.93 6.66 46.75 14.98
3 � CHOP + 2 � VIPE + 2 � DHAP
+ HD-BEAM (4/10 to 2/11)
03.2011 1241.66 60.56 32.04 29.77 12.26
1 � cladribine (5/11) 06.2011 1017.42 83.80 48.92 4.73 15.15
(continued on next page)
Academic
Radiology,Vol-
,No-
,-
2012
SPLENIC
PERFUSIO
N5
TABLE2.(continued)
Patient
Age(y)
Sex
Diagnosis
FirstDiagnosis
Treatm
ent
StudyDate
Splenic
Volume
BF
BV
Ktrans
MTT
13
56.6
MMCL
11.2010
2�
R-C
HOP;1�
R-D
HAP
12.2010
560.85
85.30
39.98
25.89
11.98
1�
R-D
HAP
01.2011
407.80
95.46
50.64
14.11
12.76
1�
HD+PBSCT(4/11)
05.2011
323.11
86.82
18.76
44.48
10.84
14
60.6
MMCL
03.2010
No
03.2010
2908.62
48.95
6.18
40.93
10.26
3�
R-C
HOP+2�
R-D
HAP
(4/10to
7/10)
06.2010
1069.75
88.09
39.88
67.18
10.34
B-C
LL,B
-cellchroniclymphocyticleukemia;B
F,b
loodflow;B
-NHL,B
-cellnon-H
odgkin’slymphoma;B
V,b
loodvolume;D
LBCL,d
iffuse
largeB-celllymphoma;F
L,follicularlymphoma;H
D,
high-dosechemotherapy;KNOSPE,chlorambucil,prednisolone;MCL,mantlecelllymphoma;MTT,meantransittime;PBSCT,peripheralb
loodstem
celltransplantation;PTCL-N
OS,periph-
eralT-celllymphomanototherw
isespecified;R-C
HOP,rituxim
ab,cyclophosphamide,hydroxydaunorubicin,vincristine,prednisone;R-D
HAP,rituxim
ab,dexamethaso
ne,cytarabine,
cisplatin;R-FC,rituxim
ab,fludarabine,cyclophosphamide;R-VIPE,rituxim
ab,mesna,cisplatin,etoposide;SMZL,splenicmarginalzonelymphoma;T-N
HL,T-cellnon-H
odgkin’s
lymphoma;
VACOP-B
,etoposide,doxorubicin,cyclophosphamide,vincristine,prednisone,bleomycin.
SAUTER ET AL Academic Radiology, Vol -, No -, - 2012
6
infradiaphragmatic involvement (4). Consequently, splenic
involvement in Hodgkin’s disease is responsible for a higher
stage of disease and alteration in treatment strategies. Deter-
mination of disease extent is also critical for appropriate treat-
ment planning and determining prognosis in non-Hodgkin’s
lymphomas (12). The following pitfalls often complicate diag-
nosis with CT imaging: (1) diffuse infiltration can appear
homogenously, or lymphoma lesions can be beyond the
scan resolution and might cause a uniform enhancement;
(2) diffuse and focal lymphoma infiltration can be present
next to each other, and only the focal lesions might be
detected; and (3) infarction or arciform splenic enhancement
patterns can hamper differentiation from lymphoma
infiltration.
Hence, the aim of this study was to provide an up-to-date
overview of the diagnostic performance of CT, using
functional VPCT, in detecting splenic involvement by malig-
nant hematologic diseases compared to controls and patients
with liver cirrhosis.
Most computed tomographic studies were performed in
the era of single-detector scanners and 10-mm axial slices.
Using splenic index measurements, Strijk et al (33) achieved
100% accuracy for discrimination between involved and
noninvolved spleens. Other size-based computed tomo-
graphic parameters for the detection of splenic involvement
were proposed by Daskalogiannaki et al (34), including
splenic volume and percentage change in splenic volume
at follow-up, all of them increasing the sensitivity and spec-
ificity of this technique. Nevertheless, particularly in
diffusely infiltrated spleens, tumor detection remains chal-
lenging, because a huge variety of other pathologies,
including inflammation and immunologic reaction, can
mimic involvement.
As an alternative, FDG PET has gained wide acceptance as
a very useful imaging modality in evaluating a variety of
neoplastic and inflammatory or infectious diseases. The major
advantage of FDG PETover traditional anatomic imaging is
that it depicts metabolic abnormalities, which often precede
changes at the anatomic level (35). However, for both CT
and FDG PET, the detection of focal uptake in the spleen is
always easier compared to the identification of diffuse infiltra-
tion. The degree of FDG uptake ultimately depends on the
glucose metabolism, which is known to be reduced in low-
grade lymphoma (36). Thus, the problem of detecting spleen
involvement in lymphoma has not been completely solved,
especially for low-grade hematologic malignancies.
Because VPCT-based splenic perfusion measurements
involve a completely different principle compared to glucose
use by tumor cells, the hypothesis was that tumor cell infiltra-
tion of the spleen could influence BF kinetics. Additionally,
lymphoma can induce secondary portal hypertension by
mass compression of the superior or inferior vena cava (14)
or by hepatic involvement (13). To exclude this possibility,
we determined splenic perfusion parameters both in noncir-
rhotic and cirrhotic patients. Our results yielded significant
differences in BF (95.66 vs 72.38 mL/100 mL/min), Ktrans
Figure 1. (a) Blood flow map of a patient with
peripheral T-cell lymphoma not otherwise
specified (PTCL-NOS) with splenic involvement.The black stars indicate an area with low blood
flow. (b) Corresponding [18F]-fluorodeoxyglu-
cose positron emission tomographic image ofthe patient with PTCL-NOS showing increased
FDG uptake. (c)Blood volumemap of the patient
with PTCL-NOS. Fast and slow enhancing
compartments of the spleen cause the heteroge-neous patterns. (d) Ktrans map of the patient with
PTCL-NOS. Fast and slow enhancing compart-
ments of the spleen cause the heterogeneous
patterns. (e)Mean transit time map of the patientwith PTCL-NOS. Fast and slow enhancing
compartments of the spleen cause the heteroge-
neous patterns. (f) Hematoxylin and eosin (H&E)
staining of a spleen specimen from a patientwith PTCL-NOS (magnification, 5�). The black
stars indicate a fine nodular infiltrate and
surrounding diffuse infiltrations. (g) H&E stainingof a spleen specimen from a patient with PTCL-
NOS (magnification, 5�). The black star shows
lymphomatous invasion into a trabecular artery.
Academic Radiology, Vol -, No -, - 2012 SPLENIC PERFUSION
(52.21 vs 49.12 mL/100 mL/min), and MTT (10.67 vs 13.77
seconds) between controls and patients with cirrhosis. Blom-
ley et al (22) reported similar differences between patients with
cirrhosis and normal controls using a single-slice technique.
Usually, arciform splenic enhancement detected by standard
CT represents no diagnostic challenge. However, differentia-
tion can become difficult in cases with diffuse, uniform splenic
involvement. Consequently, we analyzed splenic perfusion
7
SAUTER ET AL Academic Radiology, Vol -, No -, - 2012
parameters in patients with known lymphomatous involve-
ment of the spleen to determine its impact on perfusion
parameters. Correspondingly, BF and BV were comparatively
reduced at initial presentation as well as in untreated relapsed
lymphoma. This phenomenon is presumed to be the conse-
quence of progressive sinusoidal compression by increasing
lymphoma cell population in the cords of the white pulp
and even infiltration of the trabecular arteries (Figs 1f and
1g). Conversely, in patients with partial or complete remis-
sion, BF, BV, and Ktrans increased paralleled by a reduction
of splenic volume. Compared to controls, BF, Ktrans, and
MTT were significantly different. Interestingly, negative
correlations between splenic volume and BF and BV were
present, while splenic volume was positively correlated with
MTT. For a further illumination of the effects during therapy,
we correlated the diameters of nodular lymphoma manifesta-
tions with the splenic perfusion parameters. Highly negative
correlations were present for BF (r = �0.777, P = .000) and
BV (r = �0.500, P = .011).
These results encourage a more extensive investigation of
splenic perfusion for staging and monitoring purposes in
patients with lymphoma. Of note, our small patient cohort
included mainly low-grade lymphoma and chronic leukemia,
which are known to elude diagnosis by FDG PET and are
therefore themost promising target group for further research.
Our study had some limitations. First, the small number of
patients with malignant hematologic disease involving the
spleen did not allow a comprehensive statistical evaluation.
Second, it is expected that the degree of tumor infiltration
of spleen parenchyma should be crucial for accurate detection,
with low-grade involvement probably eluding diagnosis.
Third, we had histologic proof of spleen involvement in
only one patient after splenectomy and correlation with
FDG PET in two patients. Especially in the lymphoma group,
the volume perfusion computed tomographic scan range did
not cover the entire spleen. Larger studies dealing with this
issue are necessary to establish the real benefit of using
VPCT in this clinical setting.
CONCLUSIONS
We demonstrated that VPCT can determine splenic perfusion
under both normal and pathologic conditions, offering the
possibility to analyze microcirculatory flow kinetics
throughout the spleen parenchyma. This information may
potentially discriminate between perfusion abnormalities
related to either portal hypertension or cell infiltration.
ACKNOWLEDGMENTS
We wish to thank our technicians, Nicole Sachse and Astrid
Schreiber, for their excellent assistance. Dr Leopoldine
Kotzina of the Institute of Pathology, Klinikum Sindelfingen-
B€oblingen, kindly prepared and analyzed the histologic spleensections from one of our patients.
8
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