MEDICAL IMAGING

Abstract

The present invention relates to methods for assessing or obtaining an indication of vascular pressure associated with organs or visceral tissues of the body by using MRI imaging methods. The invention particularly relates to methods for assessing or obtaining an indication of portal hypertension using Magnetic Resonance T1, or T1 and T2* relaxometry, and T1, T2, and/or T2* mapping of the liver or spleen.

Claims

1-2. (canceled)

3. A computer-implemented method of obtaining an indication of the vascular pressure in a splanchnic vein of a subject, the method comprising the steps of: (a) determining from an MRI measurement obtained from the subject's spleen or liver, or a value derived therefrom, an indication of the pressure in the splanchnic vein of the subject, wherein the MRI measurement is T1 mapping or T1 relaxometry or T1 values (ms) or T2* imaging or T2* mapping or T2* values (ms) or T2 mapping or T2 relaxometry or T2 values (ms), and wherein the determining step comprises comparing the MRI measurement obtained from the subject's spleen or liver, or a value derived therefrom, with corresponding MRI measurements obtained from one or more control subjects with defined splanchnic vein pressures, thereby obtaining an indication of the vascular pressure in the splanchnic vein of the subject.

4-7. (canceled)

8. A computer-implemented method of obtaining an indication of the pressure in the hepatic portal vein of a subject, the method comprising the steps of: (a) obtaining an MRI measurement from the subject's spleen or liver, or a value derived from therefrom; and (b) determining from the MRI measurement or value in step (a) an indication of pressure in the hepatic portal vein, wherein the MRI measurement is T1 mapping or T1 relaxometry or T1 values (ms) or T2* imaging or T2* mapping or T2* values (ms) or T2 mapping or T2 relaxometry or T2 values (ms).

9. A computer-implemented method of obtaining an indication of hypertension in a splanchnic vein of a subject, the method comprising the steps of comparing: (a) an MRI measurement obtained from the subject's spleen or liver, or a value derived therefrom; and (b) the corresponding measurement or value obtained in a control without hypertension in the splanchnic vein, wherein the MRI measurement is T1 mapping or T1 relaxometry or T1 values (ms) or T2* imaging or T2* mapping or T2* values (ms) or T2 mapping or T2 relaxometry or T2 values (ms), wherein an increase in the measurement or value obtained in step (a) compared to the corresponding measurement or value in step (b) is indicative of hypertension in the splanchnic vein of the subject.

10. A method as claimed in claim 9, wherein the splanchnic vein is the hepatic portal vein.

11. A method as claimed in claim 9 or claim 10, wherein the finding of hypertension is measured using the Hepatic Wedge Pressure (HWP), the Free Hepatic Vein Pressure (FHVP), or the Hepatic Vein Pressure Gradient (HVPG).

12-45. (canceled)

46. A method as claimed in claim 3, wherein the method further comprises the step of correction of the MRI measurement or value for iron overload or deficit from an MRI measurement of iron content obtained from the subject's liver or spleen or from an image of the subject's liver or spleen.

47. A method as claimed in claim 3, wherein the measurement is obtained from a MRI image of the liver and/or spleen or the measurement is obtained from a previously-obtained MRI image of the liver and/or spleen.

48. A method as claimed in claim 3, wherein the value is derived from MRI measurements obtained or previously-obtained from the liver and/or the spleen or from MRI measurements obtained or previously-obtained from an image of the liver and/or spleen.

49. A method as claimed in claim 48, wherein the value is derived from MRI measurements obtained from the subject's spleen and liver; preferably, wherein the value is derived from or based on the sum of the T1 and/or T2* measurements obtained from the subject's spleen and liver; and more preferably, the value is the sum of the T1 measurements obtained from the subject's spleen and liver.

50-51. (canceled)

52. A method as claimed in claim 3, wherein the subject: (i) has liver disease, preferably one with liver fibrosis or liver cirrhosis; (ii) has liver disease and portal hypertension, preferably one with cirrhosis or liver fibrosis; (iii) has portal hypertension, preferably one with non-cirrhotic portal hypertension or pre-hepatic portal hypertension or hepatic portal hypertension or post hepatic portal hypertension; (iv) has heart disease, preferably one with right heart failure or congestive heart failure or congenital heart disease or constrictive pericarditis or tricuspid valve disease or valvular heart disease; (v) has liver disease that is a consequence of heart disease, preferably one with cardiac liver cirrhosis; or (vi) has increased central venous pressure.

53-55. (canceled)

56. A method as claimed in claim 8, wherein the method further comprises the step of correction of the MRI measurement or value for iron overload or deficit from an MRI measurement of iron content obtained from the subject's liver or spleen or from an image of the subject's liver or spleen.

57. A method as claimed in claim 8, wherein the measurement is obtained from a MRI image of the liver and/or spleen or the measurement is obtained from a previously-obtained MRI image of the liver and/or spleen.

58. A method as claimed in claim 8, wherein the value is derived from MRI measurements obtained or previously-obtained from the liver and/or the spleen or from MRI measurements obtained or previously-obtained from an image of the liver and/or spleen.

59. A method as claimed in claim 58, wherein the value is derived from MRI measurements obtained from the subject's spleen and liver; preferably, wherein the value is derived from or based on the sum of the T1 and/or T2* measurements obtained from the subject's spleen and liver; and more preferably, the value is the sum of the T1 measurements obtained from the subject's spleen and liver.

60. A method as claimed in claim 8, wherein the subject: (i) has liver disease, preferably one with liver fibrosis or liver cirrhosis; (ii) has liver disease and portal hypertension, preferably one with cirrhosis or liver fibrosis; (iii) has portal hypertension, preferably one with non-cirrhotic portal hypertension or pre-hepatic portal hypertension or hepatic portal hypertension or post hepatic portal hypertension; (iv) has heart disease, preferably one with right heart failure or congestive heart failure or congenital heart disease or constrictive pericarditis or tricuspid valve disease or valvular heart disease; (v) has liver disease that is a consequence of heart disease, preferably one with cardiac liver cirrhosis; or (vi) has increased central venous pressure.

61. A method as claimed in claim 9, wherein the method further comprises the step of correction of the MRI measurement or value for iron overload or deficit from an MRI measurement of iron content obtained from the subject's liver or spleen or from an image of the subject's liver or spleen.

62. A method as claimed in claim 9, wherein the measurement is obtained from a MRI image of the liver and/or spleen or the measurement is obtained from a previously-obtained MRI image of the liver and/or spleen.

63. A method as claimed in claim 9, wherein the value is derived from MRI measurements obtained or previously-obtained from the liver and/or the spleen or from MRI measurements obtained or previously-obtained from an image of the liver and/or spleen.

64. A method as claimed in claim 63, wherein the value is derived from MRI measurements obtained from the subject's spleen and liver; preferably, wherein the value is derived from or based on the sum of the T1 and/or T2* measurements obtained from the subject's spleen and liver; and more preferably, the value is the sum of the T1 measurements obtained from the subject's spleen and liver.

65. A method as claimed in claim 9, wherein the subject: (i) has liver disease, preferably one with liver fibrosis or liver cirrhosis; (ii) has liver disease and portal hypertension, preferably one with cirrhosis or liver fibrosis; (iii) has portal hypertension, preferably one with non-cirrhotic portal hypertension or pre-hepatic portal hypertension or hepatic portal hypertension or post hepatic portal hypertension; (iv) has heart disease, preferably one with right heart failure or congestive heart failure or congenital heart disease or constrictive pericarditis or tricuspid valve disease or valvular heart disease; (v) has liver disease that is a consequence of heart disease, preferably one with cardiac liver cirrhosis; or (vi) has increased central venous pressure.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0189] FIG. 1 shows the steps for choosing a liver Region of Interest (ROI) in transverse T1 and T2* maps of the abdomen. The region of interest was placed on the same location in the T1, R.sup.2 (quality assurance component of T1 mapping) and T2* maps as illustrated here. The number of pixels, area, minimum, maximum, mean and standard deviation for each region of interest (ROI) are automatically read by the scanner console software. The mean T1 and T2* value for each ROI was used in the final analysis.

[0190] FIG. 2 shows the associations between spleen T1 and (a) Hepatic Venous Pressure Gradient (HVPG) and (b) Hepatic Wedge Pressure (HWP).

[0191] FIG. 3 shows that spleen T2* could identify patients with clinically significant portal hypertension (HVPG 10 mmHg). The median spleen T2* for patients with HVPG 10 mmHg was 37.2 ms compared to 22.9 ms for patients with a HVPG<10 mmHg (p=0.036). HVPG: Hepatic Vein Pressure Gradient

[0192] FIG. 4 shows associations between Liver T1 and (a) Hepatic Venous Pressure Gradient (HVPG) and (b) Hepatic Wedge Pressure (HWP).

[0193] FIG. 5 shows that spleen T1 measurements in patients with a normal spleen iron (defined as a spleen T2*>19 ms) show a highly significant association with histological assessment of liver fibrosis.

[0194] FIG. 6 shows that spleen T1 values for patients with low spleen iron (T2*>19 ms). Mean±SD for spleen T1 for each group is as follows: Ishak 0-2:1278 ms±103; Ishak 3-4: 1325 ms±82 and Ishak 5-6: 1439 ms±72. One way analysis of variance with Bonferroni's correction showed significant differences between Ishak 5-6 and Ishak 0-2 and Ishak 3-4 (Table 1).

[0195] FIG. 7 shows that the sum of spleen T1 and liver corrected T1 measurements in patients with a normal spleen iron (defined as a spleen T2*>19 ms) show a highly significant association with histological assessment of liver fibrosis.

[0196] FIG. 8 shows liver cT1 and sinusoidal dilatation in patients with Hepatitis C. The images in the top row show transverse (a) T1 and (b) T2* maps in a patient with Hepatis C and mild fibrosis (Ishak 1). The images in the bottom row show transverse (c) T1 and (d) T2* maps from a patient with Hepatitis C, mild fibrosis (Ishak 1) and sinusoidal dilatation which is a finding indicative of vascular congestion in the liver. The values measured in a region of interest on the right lobe are shown for each image and the corrected T1 (cT1) is shown on the far right for each patient. This demonstrates that the presence of sinusoidal dilatation when other factors are equal (e.g. degree of fibrosis and underlying liver pathology-hepatitis C in this case) leads to increases in the liver corrected T1 values.

[0197] FIG. 9 shows liver cT1 and sinusoidal dilatation in patients with Primary Sclerosing Cholangitis (PSC). The images in the top row show transverse (a) T1 and (b) T2* maps in a patient with PSC and mild fibrosis (Ishak 1). The images in the bottom row show transverse (c) T1 and (d) T2* maps from a patient with PSC, mild fibrosis (Ishak 1) and sinusoidal dilatation. The values measured in a region of interest on the right lobe are shown for each image and the corrected T1 (cT1) is shown on the far right for each patient. Again, this demonstrates that the presence of sinusoidal dilatation when other factors are equal (e.g. degree of fibrosis and underlying liver pathology—PSC in this case) leads to increases in the liver corrected T1 values.

EXAMPLES

[0198] The present invention is further illustrated by the following Examples, in which parts and percentages are by weight and degrees are Celsius, unless otherwise stated. It should be understood that these Examples, while indicating preferred embodiments of the invention, are given by way of illustration only. From the above discussion and these Examples, one skilled in the art can ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions. Thus, various modifications of the invention in addition to those shown and described herein will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

[0199] The disclosure of each reference set forth herein is incorporated herein by reference in its entirety.

Example 1: Liver and Spleen T1 and T2* Mapping Using MRI can Help in the Evaluation of Portal Pressure

Background

[0200] The accumulation of liver fibrosis leads to increased hepatic vascular resistance and portal hypertension. Once portal hypertension is established in the context of liver disease, the patient is at risk of complication including, variceal bleeding, ascites, encephalopathy and renal dysfunction. Furthermore the degree of portal hypertension has important prognostic implications in many clinical situations including alcoholic hepatitis, (Rincon et al. (2007)), liver cirrhosis, (Ripoll et al. (2005)) and recent variceal bleeding (Patch et al. (1999)).

[0201] Portal pressure is usually assessed by measuring the Hepatic Vein Pressure Gradient (HVPG), which is invasive, costly and requires high expertise. Non invasive ways to assess portal hypertension have the potential to revolutionise the care of patients with liver disease as they would allow widespread use and repeated measurements to assess the progression/regression of portal hypertension over time.

[0202] A novel MRI technique has been developed for imaging the liver and spleen based on the following hypothesis: [0203] 1. The spleen parenchyma undergoes changes which may be assessed using MRI (T1 and T2* mapping) and which may indicate the severity of portal hypertension. [0204] 2. The severity of liver fibrosis as measured by liver T1 mapping would reflect the severity of portal hypertension.

[0205] Methods

[0206] Patient Population and Study Design

[0207] A prospective study was conducted to assess the MR method in the evaluation of patients with portal hypertension due to chronic liver disease. The designated reference standard was the Hepatic Vein Pressure Gradient. Patients with suspected liver cirrhosis who were due to have a liver biopsy as part of their clinical care were invited to have their biopsy through the trans-jugular route with portal pressure assessment at the time of the biopsy. Patients with portal vein thrombosis and with contra-indications to MR scanning were excluded. Eleven patients were recruited in the study period (July 2013-March 2014). The patients attended for an MRI scan prior to their biopsy.

[0208] MRI Assessment

[0209] All MR scans were performed in Oxford, UK, with the patient lying supine in a 3 Tesla system (Tim Trio, Siemens Healthcare, Germany). Patients attended for their scans having fasted for at least 4 hours. Transverse T1 and T2* maps of the abdomen were acquired and T1 and T2* measurements were documented for the liver and spleen.

[0210] Transverse Abdominal T1 Map

[0211] A T1 relaxation time map was acquired using the Shortened Modified Look Locker Inversion recovery (shMOLLI) sequence (Piechnik et al, J Cardiovasc Magn Reson) in a transverse plane through the liver and the spleen. A subject-dependent frequency adjustment was carried out during end-expiration. The ShMOLLI sequence samples the T1 recovery curve using single-shot steady state free precession (SSFP) acquisitions using the following parameters:

[0212] TR 2.14 ms, TE 1.07 ms, flip angle of 35°, field-of-view optimised per patient, acquisition matrix 192×134-160, depending on patient, with GRAPPA acceleration of 2 with 24 reference lines, yielding a typical interpolated voxel size 0.9×0.9×8 mm. Images were acquired 200 ms after the ECG R-wave and the total time for each SSFP acquisition between 169 and 197 ms, depending on the number of phase encoding steps. The variable acquisition parameters fall in the ranges used in myocardial T1 mapping at 1.5 T, with associated inter-individual coefficient of variation for normal myocardial T1 of 2.2%, (Piechnik et al, J Cardiovasc Magn Reson) well within the inter-subject coefficient of variation measured in normal volunteers here of 7%.

[0213] Transverse Abdominal T2* Mapping

[0214] A multi-gradient-echo acquisition with RF spoiling is used to calculate a T2* map of the liver. The same field-of-view as in the T1 mapping sequence is used, with a matrix size of 192×128-160, depending on patient, slice thickness of 3 mm and 2× GRAPPA acceleration, with the same 200 ms delay after the R-wave before acquisition. The image is acquired in nine segments with a TR of 26.5 ms and flip angle of 20°. Echo times are selected as far as possible such that the signals from fat and water are in phase (TE=2.46, 7.38, 12.30, 17.22 and 22.14 ms). Fat-saturation and a double-inversion-recovery black blood preparation are used.

[0215] Region of Interest Placement—Liver

[0216] A single Region of Interest (ROI) was selected for each patient. There were 4 considerations in the choice of the ROI:

[0217] (a) As each acquisition generates an R.sup.2 map for the fit of signal intensity to the exponential recovery curve the ROI was chosen in an area where R.sup.2 was 99% (which was the case in all patients),

[0218] (b) The ROI was placed approximately halfway between the porta hepatis and the liver surface in order to avoid interference from the fluid filled structures in the porta hepatis and subcutaneous tissue or air close to the liver surface,

[0219] (c) The ROI was placed so as to avoid visible bile ducts and blood vessels,

[0220] (d) The ROI was placed in an area that corresponded to good quality images in the T2* map in order to allow T1 and T2* quantification in the same ROI.

[0221] FIG. 1 illustrates the process of choosing an ROI for the liver.

[0222] Region of Interest Placement—Spleen

[0223] The choice of the ROI for the spleen followed the same principles as described above for the liver. The ROI placement in the spleen was less complicated as the spleen is smaller, and more homogeneous than the liver. It also has no blood vessels running through its parenchyma and the step of avoiding blood vessels and bile ducts as described above for the liver (step (d) above) did not apply to the spleen.

[0224] MR Image Analysis

[0225] Data were analysed by physicians blinded to the clinical information, using software tools available on the scanner console. For each patient one ROI was selected for the liver and one ROI for the spleen and mean T1 and T2* were recorded for each.

[0226] Assessment of Portal Pressures

[0227] The assessment of the portal pressures was performed by a consultant interventional radiologist specialising in hepatobiliary procedures. The procedures were carried out with the patient in the supine position, under conscious sedation, after an overnight fast. After injection of local anaesthetic in the skin, a vascular catheter was inserted through an introducer into the right internal jugular vein under ultrasound guidance. This catheter was advanced into the right atrium and then the hepatic vein to measure the right atrial pressure and free hepatic vein pressure (FHVP) respectively. The catheter was then further advanced into the wedged position where the Hepatic Wedge Pressure (HWP) was taken. The Hepatic Vein Pressure Gradient was calculated as the difference between the FHVP and the HWP.

[0228] The Hepatic Vein Pressure Gradient was used to classify portal hypertension according to this schema: HVPG<5 mmHg: No portal hypertension, HVPG 6-9 mmHg: Pre-clinical portal hypertension, HVPG≥10 mmHg: Clinically significant portal hypertension, HVPG≥12 mmHg: severe portal hypertension

[0229] Statistics

[0230] Pearson's correlation and linear regression analysis was used to check for associations between variables. Summary data for each of the HVPG categories were calculated and the Mann Whitney test was used to test for differences between the groups.

[0231] Results

[0232] Spleen T1

[0233] We found a highly significant association both between the HVPG (r=0.83; p=0.003, R.sup.2=0.69) and the HWP (r=0.88; p=0.0009; R.sup.2=0.77) and the spleen T1 relaxation time (FIG. 2).

[0234] Spleen T2*

[0235] Significant differences in the spleen T2* were found between those patients with a HVPG≥10 mmHg (median 37.2 ms; IQR 30.2-76.2) and those with a HVPG<10 mmHg (median 22.9 ms; IQR 14.6-24.5; p=0.036; FIG. 3)

[0236] Liver T1

[0237] We found a statistically significant association both between the HVPG (r=0.63; p=0.049, R.sup.2=0.40) and the HWP (r=0.68; p=0.029; R.sup.2=0.47) and the liver T1 relaxation time (FIG. 4).

Example 2: Spleen T1 and T2* Mapping can be Used to Help in the Assessment of Liver Fibrosis

[0238] Background

[0239] Changes in the severity of liver disease can result in structural and other changes in the spleen. This is particularly true for the late stages of liver disease, when portal hypertension is established. The spleen becomes engorged with portal venous blood and can be enlarged. This can be picked up on clinical examination or by using routine ultrasound scans. However, it is not known if the spleen undergoes any changes in the early stages of liver fibrosis. We hypothesised that our MR techniques for measuring spleen T1 and T2* are very sensitive and may be able to detect early changes in the spleen that occur before portal hypertension is established.

[0240] Methods

[0241] Study Design and Population

[0242] A prospective study of a new diagnostic MR method to evaluate the severity of liver fibrosis was conducted. The designated reference standard was histological assessment of liver fibrosis. From March 2011 to March 2014, patients referred for liver biopsy in Oxford were invited to take part in the study. Patients with contraindications for MR scanning and patients that were found to have an increased amount of iron in their spleen were excluded. A patient was considered to have an increased spleen iron if the measured T2* value was less than 19 ms. Patients attended for an MRI scan prior to their liver biopsy.

[0243] The MRI procedure for the acquisition and recording of liver T1 and T2* and spleen T1 and T2* is the same as described in example 1. In addition, an algorithm was used to correct the liver T1 values for the amount of iron present to produce the corrected T1 metric (cT1; Banerjee et al, J Hepatol).

[0244] Histological Interpretation of Liver Biopsies.

[0245] The Ishak score (Ishak et al, J Hepatol) was used for the histological assessment of liver fibrosis. In this score fibrosis is scored on a scale from 0 (no fibrosis) to 6 (severe fibrosis; cirrhosis). In clinical practice patients can be subdivided into 3 groups according to their Ishak score. (Ishak 0-2: no or mild fibrosis; Ishak 3-4: moderate fibrosis; Ishak 5-6 advanced fibrosis).

[0246] Statistics

[0247] Spearman's correlation coefficient was used to test for associations between the Ishak stages and spleen T1 and the sum of spleen T1 and liver cT1. One way analysis of variance (ANOVA) with Bonferroni's correction was used to test for differences between the spleen T1 and spleen T2* of those with Ishak 0-2, Ishak 3-4 and Ishak 5-6.

[0248] Results

[0249] Spleen T1

[0250] In patients with a low amount of iron in their spleen (spleen T2*>19 ms), there was a highly significant association between the spleen T1 and the degree of liver fibrosis assessed by histology (r.sub.s=0.69; p<0.000; FIG. 5).

[0251] The mean spleen T1 values of patients with severe (Ishak 5-6), moderate (Ishak 3-4) and no or mild fibrosis (Ishak 0-2) were 1439 ms, 1352 ms and 1278 ms respectively. One way ANOVA with Bonferroni's correction showed significant differences between Ishak 5-6 and Ishak 0-2 and Ishak 3-4 (FIG. 6 and Table 1).

TABLE-US-00001 TABLE 1 One way analysis of variance with Bonferroni’s correction for comparison between disease severity groups for spleen T1 Bonferroni’s Multiple Mean Significant? 95% CI Comparison Test Diff. t P < 0.05? of diff 0-2 vs 3-4 −47.26 1.135 No −150.9 to 56.38   0-2 vs 5-6 −161.0 5.401 Yes −235.2 to −86.80 3-4 vs 5-6 −113.7 2.561 Yes −224.3 to −3.202

TABLE-US-00002 TABLE 2 One way analysis of variance with Bonferroni’s correction for comparison between disease severity groups for spleen T2* Bonferroni’s Multiple Mean Significant? 95% CI Comparison Test Diff. t P < 0.05? of diff 0-2 vs 3-4 −1.219 0.2465 No −13.36 to 10.92   0-2 vs 5-6 −19.17 4.071 Yes −30.72 to −7.614 3-4 vs 5-6 −17.95 3.060 Yes −32.34 to −3.557

[0252] Sum Liver cT1 and Spleen T1

[0253] There was a highly significant correlation between the sum of spleen T1 and liver cT1 with the Ishak fibrosis score (r.sub.s=0.72; p<0.0001, FIG. 7). The correlation of the sum was stronger than the correlation of spleen T1 and Ishak score (r.sub.s=0.69; p<0.0001; FIG. 5) or between liver cT1 and Ishak (r.sub.s=0.61, p<0.0001; data not shown)

Example 3: Liver T1 Measurements can Help Evaluate Vascular Congestion in the Liver

[0254] Background

[0255] Liver vascular congestion can result from liver venous outflow tract obstruction or from any cause of increased central venous pressure (e.g. right heart failure, congestive heart failure, constrictive pericarditis, obstruction in the intra-thoracic inferior vena cava). Vascular congestion in the liver manifest as liver sinusoidal dilatation which is detected on liver biopsies. We hypothesised that liver T1 and corrected T1 would be higher in patients who have sinusoidal dilatation on liver biopsies, compared to patients without.

[0256] Methods

[0257] Pairs of patients with the same Ishak stage and the same underlying liver disease aetiology were identified from the cohort of patients in the studies of examples 1 and 2. The liver T1 and corrected T1 values of the patient pairs were compared to establish if the presence of sinusoidal dilatation had any impact on the observed measurements.

[0258] Results

[0259] We found that the presence of sinusoidal dilatation leads to an increase in the liver T1 and corrected T1. FIG. 8 illustrates a comparison between two patients with Hepatitis C and mild fibrosis (Ishak 1), where one doesn't have sinusoidal dilatation (top row, panels a and b) the other does (bottom row, panels d and c). FIG. 9 illustrates the same situation in two patients with Primary Sclerosing Cholangitis. In both scenarios, the patient where sinusoidal dilatation is present has higher liver T1 and cT1 measures.

Example 4: Example of how to Assess Central Venous Pressure Using Imaging of the Liver

[0260] Background

[0261] The liver is directly connected to the heart via the hepatic veins and the inferior vena cava. Any pathological process that leads to an increased central venous pressure can result in increased liver vascular congestion. Increases in central venous pressure can be seen in right heart failure, congestive heart failure, constrictive pericarditis and congenital heart disease.

[0262] Other causes of liver vascular congestion include liver veno-occlusive disease and venous outflow tract obstruction. Over the long term, liver vascular congestion from any cause can lead to the accumulation of fibrosis and the development of cirrhosis and liver failure.

[0263] A way of assessing liver congestion non-invasively would allow clinicians to monitor both the progression of the underlying condition causing liver congestion (e.g. right heart failure), but also the direct effect on the liver.

[0264] Liver T1 and T2* mapping and the corrected T1 metric may be used to assess liver vascular congestion and studies are designed to test this in the context of right heart failure.

[0265] Methods

[0266] Patients who are having routine clinical investigations for the evaluation of central venous pressure and right heart function are recruited. Patients have a liver MRI for T1 and T2* mapping and measurement of liver cT1 in addition to their clinically indicated investigations which may include echocardiography, cardiac MRI and cardiac catheter studies.

[0267] Association between parameters of central venous pressure and right heart function measured on echocardiography, cardiac MRI and cardiac catheter studies and Liver T1 and cT1 are tested.

[0268] The echocardiographic parameters include: [0269] 1. Right ventricular diameter [0270] 2. Pulmonary artery pressure [0271] 3. Presence and degree of tricuspid regurgitation

[0272] The MRI parameters of include: [0273] 1. Right ventricular Ejection Fraction [0274] 2. Right ventricular end systolic and end diastolic volume [0275] 3. Right ventricular end systolic and end diastolic diameter

[0276] The cardiac catheter parameters include [0277] 1. Right atrial pressure [0278] 2. Pulmonary artery pressure [0279] 3. Pulmonary wedge pressure [0280] 4. Right ventricle end systolic and end diastolic pressure [0281] 5. Right ventricle end systolic and end diastolic volume [0282] 6. The difference between the LV end diastolic pressure and the hepatic wedge pressure.

REFERENCES

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