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DOI: 10.1055/a-2357-9741
Age and gender differences of normative values of spleen diffusion MRI parameters
Alters- und Geschlechtsunterschiede der normativen Werte der Diffusions-MRT-Parameter der Milz- Abstract
- Zusammenfassung
- Introduction
- Materials and Methods
- Results
- Discussion
- Data statement
- References
Abstract
Purpose
This study investigates age and gender differences of normative values of spleen diffusion MRI parameters.
Materials and Methods
We recruited 124 volunteers with MRI conducted at 1.5T. Diffusion imaging had b-values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, 600 s/mm2. ADC, IVIM-Dslow, IVIM-PF, IVIM-Dfast, and DDVD (diffusion-derived vessel density) were computed. DDVD is the signal difference between the b=0 s/mm2 image and b=2, 4 s/mm2 image. Only images without apparent artifacts and with good curving fitting were included in the analysis. Finally, 34 females (age: 20–71 years) and 69 males (22–70 years) were measured with ADC; 20 females (20–71 years) and 48 males (22–67 years) were measured with IVIM; 32 females (20–71 years) and 65 males (22–70 years) were measured with DDVD parameter.
Results
An age-related decrease in ADC was noted for females, while such a trend was not noted for males. A very high level of heterogeneity was noted for the data for the males, with the highest ADC value being 1.710 × 10–3mm 2/s and the lowest ADC value being 0.705 × 10–3 mm2/s when b=0 and 600 s/mm 2 were used for ADC calculation. A male-female data comparison did not show a statistically significant difference between the ADC median value. However, ADCs > 1.3 × 10–3 mm2/s were only seen among males. A very high level of heterogeneity was also noted for males’ Dslow, with the highest value being 1.468 × 10–3 mm2/s and the lowest value being 0.600 × 10–3 mm2/s. Both PF and Dfast demonstrated a trend of age-related increase for older subjects. PF values were higher among males than females. However, no difference was noted for Dfast between males and females. DDVD did not show an age-related trend both for females and males. No difference was noted in DDVD values between males and females.
Conclusion
Interpreting normal spleen diffusion MRI parameters should consider age and gender factors.
Key Points
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An age-related decrease in spleen ADC and IVIM-Dslow was seen for healthy females.
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There is a high level of heterogeneity for spleen ADC and IVIM-Dslow data for healthy males.
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IVIM modelled perfusion fraction and Dfast demonstrate an artificial trend of age-related increase for older subjects.
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Vessel density measured on diffusion imaging does not show an age-related trend.
Citation Format
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Yu W, Ma FZ, Huang H et al. Age and gender differences of normative values of spleen diffusion MRI parameters. Rofo 2025; 197: 535–545
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Zusammenfassung
Zweck
Diese Studie untersucht Alters- und Geschlechtsunterschiede der normativen Werte der Diffusions-MRT-Parameter der Milz.
Materialien und Methoden
Wir rekrutierten 124 Freiwillige für eine MRT-Untersuchung mit 1.5T. Die Diffusionsbildgebung hatte b-Werte von 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, 600 s/mm2. ADC, IVIM-Dslow, IVIM-PF, IVIM-Dfast und DDVD (diffusionsabgeleitete Gefäßdichte) wurden berechnet. DDVD ist die Signaldifferenz zwischen dem Bild mit b=0 s/mm2 und dem Bild mit b=2, 4 s/mm2. In die Analyse wurden nur Bilder ohne erkennbare Artefakte und mit guter Kurvenanpassung einbezogen. Schließlich hatten 34 Frauen (Alter: 20-71 Jahre) und 69 Männer (22-70 Jahre) ADC; 20 Frauen (20-71 Jahre) und 48 Männer (22-67 Jahre) hatten IVIM; 32 Frauen (20-71 Jahre) und 65 Männer (22-70 Jahre) hatten DDVD.
Ergebnisse
Bei Frauen wurde ein altersbedingter Rückgang des ADC festgestellt, während bei Männern kein solcher Trend zu beobachten war. Bei den Daten der Männer wurde ein sehr hohes Maß an Heterogenität festgestellt, wobei der höchste ADC-Wert 1.710 × 10–3 mm2/s und der niedrigste ADC-Wert 0.705 × 10–3 mm2/s betrug, wenn b=0 und 600 s/mm2 für die ADC-Berechnung verwendet wurden. Ein Datenvergleich zwischen Männern und Frauen ergab keinen statistisch signifikanten Unterschied zwischen dem ADC-Medianwert. Allerdings wurden ADCs >1.3 × 10–3 mm2/s nur bei Männern beobachtet. Ein sehr hohes Maß an Heterogenität wurde auch für den Dslow der Männer festgestellt, wobei der höchste Wert bei 1.468 × 10–3 mm2/s und der niedrigste Wert bei 0.600 × 10–3 mm2/s lag. Sowohl PF als auch Dfast zeigten einen Trend zu einem altersbedingten Anstieg bei älteren Probanden. Die PF-Werte waren bei Männern höher als bei Frauen. Für Dfast wurde jedoch kein Unterschied zwischen Männern und Frauen festgestellt. DDVD zeigte weder bei Frauen noch bei Männern einen altersbedingten Trend. Es wurde kein Unterschied bei den DDVD-Werten zwischen Männern und Frauen festgestellt.
Schlussfolgerung
Bei der Interpretation normaler Diffusions-MRT-Parameter für die Milz sollten Alters- und Geschlechtsfaktoren berücksichtigt werden.
Kernaussagen
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Bei gesunden Frauen besteht in der eine altersbedingte Abnahme von Milz-ADC und IVIM-Dslow.
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Es besteht ein hohes Maß an Heterogenität für die ADC- und IVIM-Dslow-Daten in der Milz gesunder Männer.
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Die von IVIM modellierte Perfusionsfraktion und Dfast zeigen einen artifiziellen Trend einer altersbedingten Zunahme bei älteren Probanden.
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Die mittels Diffusionsbildgebung gemessene Gefäßdichte zeigt keinen altersbedingten Trend.
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Keywords
Apparent diffusion coefficient - Intravoxel incoherent motion (IVIM) - spleen - aging - normative valueIntroduction
The liver and spleen are the two biggest solid organs in the upper abdomen. Diffusion weighted imaging (DWI) has been applied to these organs, particularly in the oncological setting. For quantification, ADC (apparent diffusion coefficient) is already in widespread use, while IVIM (intravoxel incoherent motion) imaging remains in a research setting. Common malignant lesions of the spleen include metastases, lymphoma and leukemia. Benign lesions of the spleen include cystic lesions, infective lesions, and inflammatory pseudotumor. Though much of the published research has been focused on the liver with the spleen receiving less attention, diffusion imaging of the spleen is still commonly conducted [1] [2] [3]. Diffusion measurement from a healthy spleen is also used to normalize the measures of other abdominal organs such as the liver and pancreas [4].
Upper abdominal organ IVIM quantification has been generally considered to suffer from measurement instability [5]. With the goal to improve the stability of liver IVIM parameters, a number of measures have been adopted. For data acquisition, a 16 b-value IVIM protocol has been used [5]. Before image processing, an image data quality assessment is conducted, with images with severe respiratory motion or artifacts discarded [6]. Then, the signal is measured on the liver with an ROI (region-of-interest) based approach. The ROI-based analysis offers better parameter estimation than pixelwise fitting when the signal-to-noise ratio is low [7]. If segmented fitting is applied, a threshold b-value of 60 s/mm2 is chosen [8]. In liver IVIM parameter calculation, b=0 image data is not included for bi-exponential curve fitting [5] [9] [10]. The relationship between liver DWI signal and b-value below a diffusion weighting of 1000 s/mm2 does not follow bi-exponential decay; instead, it can be better fitted by an addition of a very fast component with a tri-exponential decay model [11]. However, with image data acquired from routine clinical scanners, the fitting of a tri-exponential decay model can be quite unstable at individual study subject’s levels [11 ]. With fitting starting from a non-zero low b-value, the relationship between DWI signal and b-value better follows a bi-exponential decay pattern [5] [10] [12]. Datasets with unacceptable curve fitting are also excluded [6]. With these approaches, good scan-rescan stability for liver IVIM can be achieved. In two studies conducted on 1.5T and 3.0T scanners, scan-rescan repeatability intraclass correlation coefficients (ICC) for IVIM-PF (perfusion fraction) of 0.837 and 0.824, respectively, in the same scan session were achieved [10] [13]. In one study conducted on a 3.0T scanner, a scan-rescan reproducibility ICC of 0.738 for PF in two different scan sessions was achieved [10]. Based on the approaches, in three clinical studies of medium sample size, a high detection rate for even early-stage liver fibrosis was achieved [5] [12].
It has been noted that there are age and gender differences in normative values of liver diffusion parameters, with older subjects being associated with a lower ADC and IVIM-Dslow, and older females being associated with lower blood perfusion [8] [14] [15] [16]. The liver and spleen are both large solid organs with rich blood supply, both are susceptible to respiratory motion, and both function as an iron storage organ. With careful imaging data processing as described above, we aim in this study to evaluate potential age and gender differences in normative values of spleen diffusion parameters. Reliable normative values are essential, particularly for the assessment of diffused spleen lesions and when using diffusion measurement from a healthy spleen to normalize measured values of other organs.
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Materials and Methods
The MRI data acquisition from healthy volunteers was approved by the institutional ethical committee, and informed consent was obtained for all subjects ([Fig. 1]). All study participants were known to be healthy at the time of the MRI exam and at the 6-month follow-up after the exam, with no liver, spleen, or other abdominal organ disease history, and with no regular medication intake. Dataset 1 was acquired in the period from Apr 22, 2019 to Dec 11, 2019. Study subjects were scanned twice during the same session as long as the study subject was able to tolerate being in the magnet and was able to lie still, with the subjects’ position and selected scan planes remaining unchanged. Imaging used a 1.5T magnet ([Table 1]) The IVIM imaging b-value selection was based on the following considerations: 1) in most clinical scanners, the maximum b-value number allowed is 16; 2) images with b-value > 600 s/mm2 tend to be too noisy; 3) to densely sample images with b-value <10s/mm2 to model the initial fast signal decay, and 4) to relatively densely sample images with b-values around 60 s/mm2 which is the critical point to separate a fast component and a slow component in perfusion-rich organs such as the liver and spleen [8] [12]. Dataset 2 was acquired during the period from Jan. 9, 2021 to Dec. 6, 2022, using the same scanner and same IVIM protocol, with the goal of sampling more older male subjects. Dataset 3 was acquired during the period from Dec. 1, 2019 to July 23, 2021, using a 3.0T scanner ([Table 1]). For all scans, participants were asked to fast for 6 hours before imaging.


Image segmentation was conducted with ITK-SNAP (http://www.itksnap.org) and data analysis was implemented in MATLAB (MathWorks, Natick, MA, USA). Blinded to the demographic information of the image data, ROI placement was conducted initially by a radiology trainee, then was checked by a senior radiologist until consensus was achieved. For ADC analysis, ROIs were placed on the b=0 s/mm2 image to cover a large portion of the spleen parenchyma while avoiding large vessels ([Fig. 2]A) and then copied to the images of other b-values (b=60 and/or b=600 s/mm2) of this slice.


ADC(b0b600) was calculated according to


where b2 and b1 refer to b=600 and b=0 s/mm2 , respectively, where S(b1) and S(b2) denote the image signal-intensity acquired at the b-factor values of b=0 and b=600 s/mm2, respectively.
ADC(b0b60b600) was calculated according to


Where bi is the ith b value(unit: s/mm2), S(bi) is the signal intensity at bi .
For IVIM analysis for Dslow (D), PF (perfusion fracture, f), and Dfast (perfusion related diffusion, D*), ROIs were placed on the b=0 image to cover a large portion of the spleen parenchyma while avoiding large vessels and then copied to the images of other b-values of this slice. IVIM parameters were calculated based on the mean signal intensity of the whole ROI. The signal value at each b-value was normalized by attributing a value of 100 at b=0 s/mm2 (S(b) norm=(S(b)/S0)×100, where S(b) and S(b)norm are the signal and normalized signal at a given b-value, respectively, S0 means the signal at b=0 s/mm2). Segmented fitting was conducted with the threshold b-value of 60 s/mm2. For the bi-compartmental model, the signal attenuation was modelled according to Eq 3:


The measurement of the spleen DDVD (diffusion-derived vessel density) followed recent reports [5] [17]. The ROI for the spleen parenchyma was segmented on the b=0 s/mm2 image (resulting in ROI area of area0) and then copied onto the b=2 s/mm2 and b=4 s/mm2 images (resulting in ROI areas of area2 and area4, respectively). The DDVD was calculated according to Eq 4–6.






For all acquired MRI data, we performed a data quality assessment prior to diffusion parameter qualification ([Fig. 1]). Images with notable motion and artifacts were initially discarded. For IVIM analysis, the quality of curve fitting was also checked, with only data with good fitting being accepted ([Fig. 2]). For the participants scanned twice, when the two scans for a subject were of good image and fitting quality, the fittings taking the mean of each b-value’s image signal were used, and if one scan was of good quality and one scan was of unacceptable quality, the scan with unacceptable quality was discarded.
For all analyses, the mean of all included slice measurements was then regarded as the value of the examination, with the last step being weighted by the ROI area of each slice. For the total of 124 subjects scanned in datasets 1 and 2, 103 subjects (83.1%) and 97 subjects (78.2%) had image data suitable for ADC and DDVD analysis, respectively, while only 68 subjects (54.8%) had image data suitable for IVIM analysis. All of dataset 3 was suitable for ADC analysis ([Fig. 1]). The total ROI areas (sum of ROI areas of all included slices) were around 60 cm2 for a study subject (supplementary table 1). For statistical analysis, data were processed using GraphPad Prism (San Diego, CA, USA). Comparisons were performed using independent 2 sample t test or Mann-Whitney U test as appropriate, and the tests were all two-sided. The significance of diffusion measures and age was tested with Pearson correlation. A p-value of less than 0.05 was considered statistically significant, > 0.1 not significant, and between 0.05 and 0.1 with a trend of significance. The liver diffusion parameter analysis of dataset 1 has been published [8]. The spleen DDVD(b0b2) results for dataset 1 have been measured and published earlier [17].
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Results
The age- and gender-related trends and differences are shown in [Table 1] and [Fig. 3], [Fig. 4], [Fig. 5], [Fig. 6].








An age-related decrease of ADC was noted for females ([Fig. 3]A, E), while for males such a trend was not noted ([Fig. 3]B, F). A very high level of heterogeneity was noted for the data for males, with the highest ADC(b0b600) value being 1.710 × 103mm2/s and the lowest value being 0.705 × 10–3mm2/s ([Fig. 3]B). A male-female data comparison did not show a statistically significant difference between the median values ([Table 1]). ADC values > 1.3 × 10–3mm2/s were only seen among males. There did not appear to be a notable difference between 1.5T ADC data and 3.0T ADC data ([Fig. 3]A, B, E, F). ADC(b0b60b600) values were systematically lower than ADC(b0b600) values (p < 0.0001 both for the data for males and the data for females, [Fig. 3]H).
An age-related decrease in Dslow was noted for females ([Fig. 4]A) but not for males ([Fig. 4]B). A very high level of heterogeneity was noted for Dslow for males, with the highest value being 1.468 × 10–3mm2/s and the lowest value being 0.600 × 10–3mm2/s. With available data, a male-female comparison did not show a statistically significant difference between the median values of Dslow ([Fig. 3]D). However, Dslow > 1.2 × 10–3mm2/s was only seen among males.
A trend of an age-related increase is noted for both PF and Dfast, and both for males and females ([Fig. 5]A, B, E, F). Statistical significance for such a trend was achieved for PF values for females (p=0.03) . A trend of marginal significance was achieved for Dfast data for males and females grouped together (p=0.09).
PF values were on average higher among males than females ([Fig. 5]C, D, P < 0.0001). However, no difference was noted for Dfast between males and females ([Fig. 5]G, H).
DDVDmean did not show an age-related trend both for females and males ([Fig. 6]A, B). No notable difference was noted in DDVDmean value between males and females ([Fig. 6]C, D).
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Discussion
Iron level and the associated T2* value in the organs are well known to influence an organ’s diffusion measurements [8] [15] [16] [18]. Both the liver and the pancreas show an age-related increase in iron deposition and a decrease in ADC [8] [15] [19]. An age-related increase in iron deposition in the spleen has also been well documented [16] [20]. Due to women’s menstruation and pregnancy, iron deposition in the liver and spleen are lower in adult pre-menopausal women than in age-matched adult men. In women, iron deposition in the liver and spleen substantially increases after menopause [20] [21]. However, a few earlier studies that attempted to investigate the potential age and gender-related changes for spleen diffusion MRI parameters reported conflicting results. Lavdas et al. [22] studied 51 healthy volunteers (mean age: 38 years; age range: 23–68 years) with a 1.5T scanner and a DWI protocol with b = 0, 150, 400, 750, and 1000 s/mm2. They noted that no significant differences for the spleen were found between males and females, and there were no significant correlations between the ADCs and age. Nazarlou and Abdolmohammadi [23] studied 69 patients (males=29, females =40, without notable spleen abnormalities) with a 1.5T scanner and a DWI protocol with b-values of 50, 400, and 800 s/mm2. The mean age was 52.5 years (age range: 11–84 years) for males and 46.8 years (age range 10–85 years) for females. They concluded that no differences were observed in ADC values of the spleen among the female and male participants or those from various ages. On the other hand, Li et al. [24] studied 127 patients (age range: 10–79 years, mean age: 44.4 years, without notable spleen abnormalities) with a 1.5T scanner and a DWI protocol with b-values of 0, 800 s/mm2. They reported an age-related decrease in ADC values for older patients. However, Li et al. did not separately analyze male and female data. Chen et al. [25] studied 1243 patients (age range: 18–91 years, mean age: 57 years, without notable spleen abnormalities) using 3.0T scanners and a DWI protocol with b-values of 50, 800 s/mm2. They reported that the spleen ADC values for the males were lower than those for the females, and the spleen ADC values increased with patient age.
With a relatively large sample size and meticulous care taken for data analysis, our study aims to clarify earlier conflicting reports. We hypothesized that for females there is an age-related decrease of ADC and Dslow for the spleen, which was confirmed in this study. However, despite the relatively large sample size, we did not see an apparent trend of age-related change for ADC and Dslow among males. On the contrary, very high ADC and Dslow values were seen in male subjects aged > 45 years. Despite the fact that the same criteria and the same care were taken to measure the data for females and males, the female results were relatively ‘clean’ and consistent with our expectations, and the results for the male spleen were very heterogeneous. We double-checked the images and the curve-fitting patterns. There was no reason for us to exclude the ‘extreme’ values in the results of males. Moreover, the two scans for each subject, when included for analysis, all showed the same pattern. Schwenzer et al. [16] reported a negative and statistically significant correlation between age and spleen T2* in healthy females (r=–0.44, P < 0.0001), and a minimally negative and statistically non-significant correlation between age and spleen T2* in healthy males (r=–0.13, P > 0.05). There was a much greater T2* variation in the spleen than in the liver, with spleen T2* varying between 14.4–113.6 ms (mean 48.3 ms) for females and 15.8–69.0 (mean: 36.1) for males, liver T2* varying between 14.7–45.96 ms (mean 29.6 ms) for females and 13.6–43.1 (mean: 25.4) for males. Our results can help to explain the results of Lavdas et al. and those of Nazarlou and Abdolmohammadi. It is more difficult to acquire satisfactory diffusion data fitting in the spleen than in the liver. For the liver, we commonly can have satisfactory IVIM diffusion data fitting for 80–85% of the scanned cases [8] [12] [13], but for the spleen satisfactory IVIM diffusion data fitting was only achieved for 54.8% of the scanned cases in this study. Compared with the liver, the spleen is substantially smaller in volume, so that fewer slices and a smaller ROI were available for signal averaging. The data fitting for ADC can also be subject to instabilities [26]. Lavdas et al. observed age-related reduction of ADC for the liver, but not for the spleen. The quality of spleen diffusion measurements can be hampered both by the difficulties in data fitting and also by their relatively small sample size with 27 females most of whom were pre-menopausal or para-menopausal [22]. For ADC, we excluded 17% of the scanned cases which were considered to be of insufficient quality. Chen et al. [25] reported spleen ADC values increased with the age of patients, which differs from the results of Li et al. and also differs from our female results. It was not described whether the studies of Lavdas et al. [22], Nazarlou and Abdolmohammadi [23], Li et al. [24], and Chen et al. [25] excluded data of insufficient quality. Note that the studies of Nazarlou and Abdolmohammadi, Li et al. and Chen et al. were all on patients. It is unknown how and whether they excluded data regarding metabolic diseases. Patients with more subtle alterations of spleen diffusion and perfusion might not have been totally excluded, for example. The data of Nazarlou and Abdolmohammadi are also likely affected by extreme values [23].
With three b-values to fit the results, ADC(b0b60b600) can be potentially more stable (i.e., with higher scan-rescan reproducibility) than ADC(b0bb600). While ADC(b0b60b600) values were systematically lower than ADC(b0bb600) values, which can be explained by the fast diffusion (perfusion) effect as shown in Supplementary Fig. 1, ADC(b0b60b600) and ADC (b0bb600) show similar age- and gender-related trends. With limited data, this study did not show a notable difference between 3.0T and 1.5T for the spleen ADC value ([Fig. 3]).
Our study is the first to investigate age and gender differences of normative values of spleen IVIM parameters. Consistent with earlier results for the liver with standard IVIM modeling [4], there were trends of an age-related increase in the spleen of older subjects both for observed PF and observed Dfast. It was reported earlier that, with standard IVIM modeling, a decrease in liver T2* value leads to an increase in observed PF, and a decrease in observed Dslow [18]. On the other hand, an increase in liver T2 value will lead to a decrease in observed PF [27]. Thus, IVIM observed PF and Dfast are not interpreted as a true physiological values in liver perfusion. Instead, they should be considered as ‘composite’ biomarkers that are still clinically meaningful [5] [12] [28] [29]. The same as the results for ADC and Dslow, a tendency is noted for the PF in the male spleen to be more heterogeneous than the PF in the female spleen. The spleen PFs in males were on average higher than the spleen PFs in females. This can be partially explained by higher iron content among males [16] [18]. IVIM observed Dslow and PF are known to be negatively correlated [8] [28] [29]. Dfast values were heterogeneous for both males and females, which is a known feature of Dfast due to its instability in data fitting [5] [11].
ADC and IVIM values have been tested for quantitative evaluation of spleen pathologies. For example, Jang et al. [1] described that the lesion-to-parenchyma ADC ratios were significantly different between malignant lesions and benign lesions. Bian et al. [2] studied spleen DWI for acute leukemia patients with splenomegaly, acute leukemia patients with normal spleen volume, and healthy controls. IVIM parameters were all significantly different among the three groups. Dslow was correlated with white blood cell counts, lactate dehydrogenase, and bone marrow blasts [2]. Klasen et al. [3] reported that compared with controls, patients with cirrhosis and portal hypertension had significantly higher spleen ADCs. There was a statistically significant correlation between Child–Pugh grade and spleen ADC. After transjugular intrahepatic portosystemic shunt implantation, a reduction in spleen ADC values was noted [3]. Note that there have been many efforts to use spleen diffusion parameters as a reference measurement to normalize the data for other abdominal organs [4]. The results in this study suggest caution should be taken for such an approach, particularly for men.
On DWI, blood vessels (including micro-vessels) show a high signal when there is no diffusion gradient (b=0 s/mm2), while they show a low signal even when very low b-values (such as b=2 or 4 s/mm2) are applied [9]. DDVD can be interpreted as a physiological surrogate of the area of micro-vessels per unit tissue area, which can be conceptually converted to a surrogate of the volume of micro-vessels per tissue unit volume if multiple slices are integrated. Zheng et al. [17] described a decreased spleen DDVD in viral hepatitis-b liver fibrosis patients. Earlier a relatively ‘clean’ decrease in liver DDVD value for older females was observed [8]. This is in agreement with the known physiological age-dependent reduction in liver blood flow. However, an earlier report did not see such a trend both for the female spleen DDVD (n=35) and the male spleen DDVD (n=32) [17]. In this study, we increased the sample size for males to n=65 and re-measured DDVDmean which is the average of DDVD(b0b2) and DDVD(b0b4) which in theory increases the stability of DDVD values. However, spleen DDVDmean still did not show an age-related change. In addition, DDVD values were more heterogeneous in the spleen than in the liver ([Fig. 2] in [17], [Fig. 3] in [8] and [Fig. 6] in this study). It is possible that the much wider variation in iron concentration in the spleen than in the liver [16] may affect the spleen DDVD value. Although physiologically, the per unit volume blood perfusion to the spleen is not less than that to the liver, IVIM measured PF is only half of that of the liver [30], and this is considered at least partially due to the higher spleen T2 relative to liver T2 [27]. Due to the much smaller PF quantified with standard IVIM [30], we included b=0 data for the IVIM curve fitting in this study.
There are many limitations to this study. We could not explore the biophysical mechanisms behind the observed trends or variation, but we think iron concentration and T2* may explain parts of the trends. Spleen iron concentration does not change a lot in male adults (or can increase slightly in older males), while spleen iron concentration increases substantially in females after menopause [16] [21] and this may cause the decrease in ADC and Dslow observed in older females. It can be argued that the sample size used in this study was small for females. However, we expect that while more samples may lead to some of the trends becoming statistically more significant, it is unlikely that the trend directions will be altered. The data were mainly collected for 1.5T, with only limited ADC data for 3.0T. Another limitation is that we do not have data for pediatric and adolescent populations where large changes can be expected. This is a healthy subject study, and we did not provide any pathologic data under the same conditions. Though we did not provide intra- and inter-observer variability data, we do not expect this will be an issue as the ROI placement for the normal spleen is reasonably straightforward.
To summarize, this study shows an age-related decrease in spleen ADC and Dslow for older females. ADC and Dslow show high heterogeneity for males. The high heterogeneity for ADC and Dslow in males suggests that it is difficult to define what values are abnormally elevated. However, the lowest normal value of ADC or Dslow appeared to be consistent among males and females, i.e., higher than 0.6 × 10–3 mm/s in this study. This study shows the normative value of PF is higher among men than among women. Due to the high instability, Dfast is not commonly used for disease assessment, and this study supports this practice for the spleen.
Clinical Relevance
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Interpretation of normal spleen ADC and IVIM parameters should take age and gender factors into consideration.
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The high heterogeneity for ADC and IVIM-Dslow in males suggests that it is difficult to define what values are abnormally elevated.
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IVIM modelled spleen perfusion fraction and Dfast demonstrate an artificial trend of an age-related increase for older subjects.
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Data statement
Raw data can be obtained by external researchers for analysis by contacting the corresponding author of this article.
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Conflict of Interest
The authors declare that they have no conflict of interest.
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References
- 1 Jang KM, Kim SH, Hwang J. et al. Differentiation of malignant from benign focal splenic lesions: added value of diffusion-weighted MRI. AJR Am J Roentgenol 2014; 203: 803-812
- 2 Bian W, Huang Q, Zhang J. et al. Intravoxel incoherent motion diffusion-weighted MRI for the evaluation of early spleen involvement in acute leukemia. Quant Imaging Med Surg 2024; 14: 98-110
- 3 Klasen J, Lanzman RS, Wittsack HJ. et al. Diffusion-weighted imaging (DWI) of the spleen in patients with liver cirrhosis and portal hypertension. Magn Reson Imaging 2013; 31: 1092-1096
- 4 Do RK, Chandarana H, Felker E. et al. Diagnosis of liver fibrosis and cirrhosis with diffusion-weighted imaging: value of normalized apparent diffusion coefficient using the spleen as reference organ. AJR Am J Roentgenol 2010; 195: 671-676
- 5 Wang YX, Huang H, Zheng CJ. et al. Diffusion-weighted MRI of the liver: challenges and some solutions for the quantification of apparent diffusion coefficient and intravoxel incoherent motion. Am J Nucl Med Mol Imaging 2021; 11: 107-142
- 6 Chevallier O, Zhou N, He J. et al. Removal of evidential motion-contaminated and poorly fitted image data improves IVIM diffusion MRI parameter scan-rescan reproducibility. Acta Radiologica 2018; 59: 1157-1167
- 7 Yuan J, Wong OL, Lo GG. et al. Statistical assessment of bi-exponential diffusion weighted imaging signal characteristics induced by intravoxel incoherent motion in malignant breast tumors. Quant Imaging Med Surg 2016; 6: 418-429
- 8 Huang H, Zheng CJ, Wang LF. et al. Age and gender dependence of liver diffusion parameters and the possibility that intravoxel incoherent motion modelling of perfusion component is constrained by diffusion component. NMR Biomed 2021; 34: e4449
- 9 Wang YX. Living tissue intravoxel incoherent motion (IVIM) diffusion MR analysis without b = 0 image: an example for liver fibrosis evaluation. Quant Imaging Med Surg 2019; 9: 127-133
- 10 Zheng CJ, Xiao BH, Huang H. et al. Bi-exponential fitting excluding b=0 data improves the scan-rescan stability of liver IVIM parameter measures and particularly so for the perfusion fraction. Quant Imaging Med Surg 2022; 12: 3288-3299
- 11 Chevallier O, Zhou N, Cercueil JP. et al. Comparison of tri-exponential decay versus bi-exponential decay and full fitting versus segmented fitting for modeling liver intravoxel incoherent motion diffusion MRI. NMR Biomed 2019; 32: e4155
- 12 Li T, Che-Nordin N, Wáng YXJ. et al. Intravoxel incoherent motion derived liver perfusion/diffusion readouts can be reliable biomarker for the detection of viral hepatitis B induced liver fibrosis. Quant Imaging Med Surg 2019; 9: 371-385
- 13 Li XM, Ma FZ, Quan XY. et al. Repeatability and reproducibility comparisons of liver IVIM imaging with free-breathing or respiratory-triggered sequences. NMR Biomed 2023; e5080
- 14 Wáng YXJ. Gender-specific liver aging and magnetic resonance imaging. Quant Imaging Med Surg 2021; 11: 2893-2904
- 15 Metens T, Ferraresi KF, Farchione A. et al. Normal hepatic parenchyma visibility and ADC quantification on diffusion-weighted MRI at 3 T: influence of age, gender, and iron content. Eur Radiol 2014; 24: 3123-3133
- 16 Schwenzer NF, Machann J, Haap MM. et al. T2* relaxometry in liver, pancreas, and spleen in a healthy cohort of one hundred twenty-nine subjects-correlation with age, gender, and serum ferritin. Invest Radiol 2008; 43: 854-860
- 17 Zheng CJ, Huang H, Xiao BH. et al. Spleen in viral Hepatitis-B liver fibrosis patients may have a reduced level of per unit micro-circulation: non-invasive diffusion MRI evidence with a surrogate marker. SLAS Technol 2022; 27: 187-194
- 18 Xiao BH, Wáng YXJ. Different tissue types display different signal intensities on b = 0 images and the implications of this for intravoxel incoherent motion analysis: Examples from liver MRI. NMR Biomed 2021; 34: e4522
- 19 Herrmann J, Schoennagel BP, Roesch M. et al. Diffusion-weighted imaging of the healthy pancreas: ADC values are age and gender dependent. J Magn Reson Imaging 2013; 37: 886-891
- 20 Sorokin EP, Basty N, Whitcher B. et al. Analysis of MRI-derived spleen iron in the UK Biobank identifies genetic variation linked to iron homeostasis and hemolysis. Am J Hum Genet 2022; 109: 1092-1104
- 21 Zacharski LR, Ornstein DL, Woloshin S. et al. Association of age, sex, and race with body iron stores in adults: analysis of NHANES III data. Am Heart J 2000; 140: 98-104
- 22 Lavdas I, Rockall AG, Castelli F. et al. Apparent Diffusion Coefficient of Normal Abdominal Organs and Bone Marrow From Whole-Body DWI at 1.5 T: The Effect of Sex and Age. AJR Am J Roentgenol 2015; 205: 242-250
- 23 Nazarlou AK, Abdolmohammadi J. A study of the relationship between gender/age and apparent diffusion coefficient values in spleen of healthy adults using diffusion-weighted magnetic resonance imaging. Electron Physician 2015; 7: 1005-1009
- 24 Li G, Xu P, Pan X. et al. The effect of age on apparent diffusion coefficient values in normal spleen: A preliminary study. Clinical radiology 2014; 69: e165-e167
- 25 Chen Y, Yang P, Fu C. et al. Variabilities in apparent diffusion coefficient (ADC) measurements of the spleen and the paraspinal muscle: A single center large cohort study. Heliyon 2023; 9: e18166
- 26 Miquel ME, Scott AD, Macdougall ND. et al. In vitro and in vivo repeatability of abdominal diffusion-weighted MRI. Br J Radiol 2012; 85: 1507-1512
- 27 Ma FZ, Wáng YXJ. T2 relaxation time elongation of hepatocellular carcinoma relative to native liver tissue leads to an underestimation of perfusion fraction measured by standard intravoxel incoherent motion magnetic resonance imaging. Quant Imaging Med Surg 2024; 14: 1316-1322
- 28 Wáng YXJ. Mutual constraining of slow component and fast component measures: some observations in liver IVIM imaging. Quant Imaging Med Surg 2021; 11: 2879-2887
- 29 Wáng YXJ. A reduction of perfusion can lead to an artificial elevation of slow diffusion measure: examples in acute brain ischemia MRI intravoxel incoherent motion studies. Ann Transl Med 2021; 9: 895
- 30 Yu WL, Xiao BH, Ma FZ. et al. Underestimation of the spleen perfusion fraction by intravoxel incoherent motion MRI. NMR Biomed 2023; 36: e4987
Correspondence
Publication History
Received: 12 April 2024
Accepted after revision: 28 June 2024
Article published online:
30 July 2024
© 2024. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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References
- 1 Jang KM, Kim SH, Hwang J. et al. Differentiation of malignant from benign focal splenic lesions: added value of diffusion-weighted MRI. AJR Am J Roentgenol 2014; 203: 803-812
- 2 Bian W, Huang Q, Zhang J. et al. Intravoxel incoherent motion diffusion-weighted MRI for the evaluation of early spleen involvement in acute leukemia. Quant Imaging Med Surg 2024; 14: 98-110
- 3 Klasen J, Lanzman RS, Wittsack HJ. et al. Diffusion-weighted imaging (DWI) of the spleen in patients with liver cirrhosis and portal hypertension. Magn Reson Imaging 2013; 31: 1092-1096
- 4 Do RK, Chandarana H, Felker E. et al. Diagnosis of liver fibrosis and cirrhosis with diffusion-weighted imaging: value of normalized apparent diffusion coefficient using the spleen as reference organ. AJR Am J Roentgenol 2010; 195: 671-676
- 5 Wang YX, Huang H, Zheng CJ. et al. Diffusion-weighted MRI of the liver: challenges and some solutions for the quantification of apparent diffusion coefficient and intravoxel incoherent motion. Am J Nucl Med Mol Imaging 2021; 11: 107-142
- 6 Chevallier O, Zhou N, He J. et al. Removal of evidential motion-contaminated and poorly fitted image data improves IVIM diffusion MRI parameter scan-rescan reproducibility. Acta Radiologica 2018; 59: 1157-1167
- 7 Yuan J, Wong OL, Lo GG. et al. Statistical assessment of bi-exponential diffusion weighted imaging signal characteristics induced by intravoxel incoherent motion in malignant breast tumors. Quant Imaging Med Surg 2016; 6: 418-429
- 8 Huang H, Zheng CJ, Wang LF. et al. Age and gender dependence of liver diffusion parameters and the possibility that intravoxel incoherent motion modelling of perfusion component is constrained by diffusion component. NMR Biomed 2021; 34: e4449
- 9 Wang YX. Living tissue intravoxel incoherent motion (IVIM) diffusion MR analysis without b = 0 image: an example for liver fibrosis evaluation. Quant Imaging Med Surg 2019; 9: 127-133
- 10 Zheng CJ, Xiao BH, Huang H. et al. Bi-exponential fitting excluding b=0 data improves the scan-rescan stability of liver IVIM parameter measures and particularly so for the perfusion fraction. Quant Imaging Med Surg 2022; 12: 3288-3299
- 11 Chevallier O, Zhou N, Cercueil JP. et al. Comparison of tri-exponential decay versus bi-exponential decay and full fitting versus segmented fitting for modeling liver intravoxel incoherent motion diffusion MRI. NMR Biomed 2019; 32: e4155
- 12 Li T, Che-Nordin N, Wáng YXJ. et al. Intravoxel incoherent motion derived liver perfusion/diffusion readouts can be reliable biomarker for the detection of viral hepatitis B induced liver fibrosis. Quant Imaging Med Surg 2019; 9: 371-385
- 13 Li XM, Ma FZ, Quan XY. et al. Repeatability and reproducibility comparisons of liver IVIM imaging with free-breathing or respiratory-triggered sequences. NMR Biomed 2023; e5080
- 14 Wáng YXJ. Gender-specific liver aging and magnetic resonance imaging. Quant Imaging Med Surg 2021; 11: 2893-2904
- 15 Metens T, Ferraresi KF, Farchione A. et al. Normal hepatic parenchyma visibility and ADC quantification on diffusion-weighted MRI at 3 T: influence of age, gender, and iron content. Eur Radiol 2014; 24: 3123-3133
- 16 Schwenzer NF, Machann J, Haap MM. et al. T2* relaxometry in liver, pancreas, and spleen in a healthy cohort of one hundred twenty-nine subjects-correlation with age, gender, and serum ferritin. Invest Radiol 2008; 43: 854-860
- 17 Zheng CJ, Huang H, Xiao BH. et al. Spleen in viral Hepatitis-B liver fibrosis patients may have a reduced level of per unit micro-circulation: non-invasive diffusion MRI evidence with a surrogate marker. SLAS Technol 2022; 27: 187-194
- 18 Xiao BH, Wáng YXJ. Different tissue types display different signal intensities on b = 0 images and the implications of this for intravoxel incoherent motion analysis: Examples from liver MRI. NMR Biomed 2021; 34: e4522
- 19 Herrmann J, Schoennagel BP, Roesch M. et al. Diffusion-weighted imaging of the healthy pancreas: ADC values are age and gender dependent. J Magn Reson Imaging 2013; 37: 886-891
- 20 Sorokin EP, Basty N, Whitcher B. et al. Analysis of MRI-derived spleen iron in the UK Biobank identifies genetic variation linked to iron homeostasis and hemolysis. Am J Hum Genet 2022; 109: 1092-1104
- 21 Zacharski LR, Ornstein DL, Woloshin S. et al. Association of age, sex, and race with body iron stores in adults: analysis of NHANES III data. Am Heart J 2000; 140: 98-104
- 22 Lavdas I, Rockall AG, Castelli F. et al. Apparent Diffusion Coefficient of Normal Abdominal Organs and Bone Marrow From Whole-Body DWI at 1.5 T: The Effect of Sex and Age. AJR Am J Roentgenol 2015; 205: 242-250
- 23 Nazarlou AK, Abdolmohammadi J. A study of the relationship between gender/age and apparent diffusion coefficient values in spleen of healthy adults using diffusion-weighted magnetic resonance imaging. Electron Physician 2015; 7: 1005-1009
- 24 Li G, Xu P, Pan X. et al. The effect of age on apparent diffusion coefficient values in normal spleen: A preliminary study. Clinical radiology 2014; 69: e165-e167
- 25 Chen Y, Yang P, Fu C. et al. Variabilities in apparent diffusion coefficient (ADC) measurements of the spleen and the paraspinal muscle: A single center large cohort study. Heliyon 2023; 9: e18166
- 26 Miquel ME, Scott AD, Macdougall ND. et al. In vitro and in vivo repeatability of abdominal diffusion-weighted MRI. Br J Radiol 2012; 85: 1507-1512
- 27 Ma FZ, Wáng YXJ. T2 relaxation time elongation of hepatocellular carcinoma relative to native liver tissue leads to an underestimation of perfusion fraction measured by standard intravoxel incoherent motion magnetic resonance imaging. Quant Imaging Med Surg 2024; 14: 1316-1322
- 28 Wáng YXJ. Mutual constraining of slow component and fast component measures: some observations in liver IVIM imaging. Quant Imaging Med Surg 2021; 11: 2879-2887
- 29 Wáng YXJ. A reduction of perfusion can lead to an artificial elevation of slow diffusion measure: examples in acute brain ischemia MRI intravoxel incoherent motion studies. Ann Transl Med 2021; 9: 895
- 30 Yu WL, Xiao BH, Ma FZ. et al. Underestimation of the spleen perfusion fraction by intravoxel incoherent motion MRI. NMR Biomed 2023; 36: e4987























