Fat Iron Cirrhosis - Scbtmr Donald Mitcgell … · Fatty Liver DiseaseFatty Liver Disease •...

Diffuse Liver Disease:MRI EvaluationDiffuse Liver Disease:Diffuse Liver Disease:MRI EvaluationMRI Evaluation

Thomas Jefferson UniversityPhiladelphia, PA

Donald G. Mitchell, M.D.

••Fat Fat ••IronIron••CirrhosisCirrhosis

Fatty Liver DiseaseFatty Liver DiseaseFatty Liver Disease• Common, increasing

» Diabetes» Diet, high fructose corn syrup, etc» Metabolic syndrome

• NASH (vs. “benign” NAFLD)» Inflammation, fibrosis» Primary cause of “cryptogenic cirrhosis”

• Goals: » Measure fat and response to intervention» Detect inflammation and early fibrosis» ? Other disease parameters (e.g. mesenteric adiposity)

•• Common, increasingCommon, increasing»» DiabetesDiabetes»» Diet, high fructose corn syrup, etcDiet, high fructose corn syrup, etc»» Metabolic syndromeMetabolic syndrome

•• NASH (vs. NASH (vs. ““benignbenign”” NAFLD)NAFLD)»» Inflammation, fibrosisInflammation, fibrosis»» Primary cause of Primary cause of ““cryptogenic cirrhosiscryptogenic cirrhosis””

•• Goals: Goals: »» Measure fat and response to interventionMeasure fat and response to intervention»» Detect inflammation and early fibrosisDetect inflammation and early fibrosis»» ? Other disease parameters (e.g. mesenteric adiposity)? Other disease parameters (e.g. mesenteric adiposity)

Fatty LiverFatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Dual Echo GRE (2D)Dual Echo GRE (2D)InIn--phase & Opposedphase & Opposed--Phase with exact same anatomyPhase with exact same anatomy

TE = 2.3 msecTE = 2.3 msec

TE = 4.6 msecTE = 4.6 msec

Fatty LiverFatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Lifestyle Change Lifestyle Change 6 mos F/U6 mos F/U

Fatty LiverFatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Nodular Fatty Infiltration

Nodular Fatty Nodular Fatty InfiltrationInfiltration

Fatty LiverFatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Fatty LiverFatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Fatty Liver Disease: MethodsFatty Liver Disease: Fatty Liver Disease: MethodsMethods

• Dual GRE (2-point Dixon)» Included in routine protocols» Confounded by iron» Ambiguity near 50% lipid signal

• 3-point Dixon» Longer acquisition» Resolves iron and other T2 differences» Algorithm should account for multiple lipid peaks

• Spectroscopy » Resolves 50% lipid ambiguity

•• Dual GRE (2Dual GRE (2--point Dixon)point Dixon)»» Included in routine protocolsIncluded in routine protocols»» Confounded by ironConfounded by iron»» Ambiguity near 50% lipid signalAmbiguity near 50% lipid signal

•• 33--point Dixonpoint Dixon»» Longer acquisitionLonger acquisition»» Resolves iron and other T2 differencesResolves iron and other T2 differences»» Algorithm should account for multiple lipid peaksAlgorithm should account for multiple lipid peaks

•• Spectroscopy Spectroscopy »» Resolves 50% lipid ambiguityResolves 50% lipid ambiguity

Fatty LiverFatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

33--Point DixonPoint Dixon

Fatty LiverFatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Fatty LiverFatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Fatty Liver Disease: 3TFatty Liver Disease: Fatty Liver Disease: 3T3T

• Dixon Techniques» Shorter TE intervals

• Spectroscopy» Greater lipid-water

separation

• Experience, Literature

•• Dixon TechniquesDixon Techniques»» Shorter TE intervalsShorter TE intervals

•• SpectroscopySpectroscopy»» Greater lipidGreater lipid--water water

separationseparation

•• Experience, Experience, Literature Literature

TE = 1.15TE = 1.15

TE = 2.3TE = 2.3

Fatty LiverFatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

• Hemochromatosis» Primary (genetic)

Phlebotomy» Erythrogenic (e.g. Thalasemia)

Ineffective erythropoiesisMay be exacerbated by transfusions

» Exogenous

• Transfusional Siderosis» Reticuloendothelial» Usually not clinically significant

• Hemolysis» Intravascular (free hemoglobin)» Extravascular (splenic)

• Cirrhosis» Mildly increased iron is common

•• HemochromatosisHemochromatosis»» Primary (genetic)Primary (genetic)

PhlebotomyPhlebotomy»» ErythrogenicErythrogenic (e.g. (e.g. ThalasemiaThalasemia))

Ineffective Ineffective erythropoiesiserythropoiesisMay be exacerbated by transfusionsMay be exacerbated by transfusions

»» ExogenousExogenous

•• TransfusionalTransfusional SiderosisSiderosis»» ReticuloendothelialReticuloendothelial»» Usually not clinically significantUsually not clinically significant

•• HemolysisHemolysis»» Intravascular (free hemoglobin)Intravascular (free hemoglobin)»» ExtravascularExtravascular ((splenicsplenic))

•• CirrhosisCirrhosis»» Mildly increased iron is commonMildly increased iron is common

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Iron Overload: MethodsIron Overload: Iron Overload: MethodsMethodsFatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

• Dual GRE (2-point Dixon)» Included in routine protocols» Confounded by lipid» Moderately sensitive

• Multi-echo GRE» Longer acquisition» Resolves lipid and other CS differences» Affected by microscopic distribution of iron» Too sensitive (can’t measure severe overload)

• Multi-echo SE» Even longer acquisition

• ?Calibration between SI to iron concentration

•• Dual GRE (2Dual GRE (2--point Dixon)point Dixon)»» Included in routine protocolsIncluded in routine protocols»» Confounded by lipidConfounded by lipid»» Moderately sensitiveModerately sensitive

•• MultiMulti--echo GREecho GRE»» Longer acquisitionLonger acquisition»» Resolves lipid and other CS differencesResolves lipid and other CS differences»» Affected by microscopic distribution of ironAffected by microscopic distribution of iron»» Too sensitive (canToo sensitive (can’’t measure severe overload)t measure severe overload)

•• MultiMulti--echo SEecho SE»» Even longer acquisitionEven longer acquisition

•• ?Calibration between SI to iron concentration?Calibration between SI to iron concentration

TE = 0.9TE = 0.9 TE = 1.7TE = 1.7

TE = 2.6TE = 2.6

TE = 4.3TE = 4.3

TE = 3.5TE = 3.5

TE = 5.2TE = 5.2

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

MultiMulti--EchoEcho

TE = 4.6TE = 4.6

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

TransfusionalSiderosisTransfusionalTransfusionalSiderosisSiderosis

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

HemochromatosisHemochromatosisHemochromatosisFatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Idiopathic Idiopathic HemochromatosisHemochromatosis

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Intravascular Hemolysis

Intravascular Intravascular HemolysisHemolysis

Sickle Cell AnemiaSickle Cell Anemia

Paroxysmal Paroxysmal Nocturnal Nocturnal

HemoglobinuriaHemoglobinuria

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Hepatitis C, NASH, etcHepatitis Hepatitis C, NASH, etcC, NASH, etc• Early Fibrosis

» Morphology» Diffusion» Elastography» Spectroscopy» Perfusion» Etc.

• Complications» HCC» Portal Hypertension» Esophageal Varices

•• Early FibrosisEarly Fibrosis»» MorphologyMorphology»» DiffusionDiffusion»» ElastographyElastography»» SpectroscopySpectroscopy»» PerfusionPerfusion»» Etc.Etc.

•• ComplicationsComplications»» HCCHCC»» Portal HypertensionPortal Hypertension»» Esophageal VaricesEsophageal Varices

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Morphologic SignsMorphologic SignsMorphologic Signs

• Nodular Contour & Texture• Peripheral Right & Medial

Atrophy / Caudate & Central Hypertrophy

» Empty GB Fossa» Wide Porta Hepatis and

Falciform Ligament» Anterolateral Flattening» Caudate/Right Lobe > 1

•• Nodular Contour & TextureNodular Contour & Texture•• Peripheral Right & Medial Peripheral Right & Medial

Atrophy / Caudate & Central Atrophy / Caudate & Central HypertrophyHypertrophy

»» Empty GB FossaEmpty GB Fossa»» Wide Porta Hepatis and Wide Porta Hepatis and

Falciform LigamentFalciform Ligament»» Anterolateral FlatteningAnterolateral Flattening»» Caudate/Right Lobe > 1Caudate/Right Lobe > 1

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Caudate / Right Lobe RatioCaudate / Right Lobe RatioCaudate / Right Lobe Ratio

MPVMPVMPV

RPVRPVRPV

X’XX’’ A’AA’’XXX AAA C/R > 0.65C/R > 0.65C/R > 0.65

C/R > 0.9C/R > 0.9C/R > 0.9C/R > 1.0C/R > 1.0C/R > 1.0

Harbin WP, Robert NJ, Harbin WP, Robert NJ, FerrucciJT. Radiology FerrucciJT. Radiology 1980; 135:2731980; 135:273--283283

Awaya H, Mitchell DG, Awaya H, Mitchell DG, et al. Radiology 2002; et al. Radiology 2002; 224:769224:769--774.774.

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Cirrhosis– Expanded GB Fossa

CirrhosisCirrhosis–– Expanded Expanded GB FossaGB Fossa

NormalNormalNormal

Early CirrhosisEarly CirrhosisEarly Cirrhosis

68% sensitive, 98% specific, 68% sensitive, 98% specific, 98% PPV for cirrhosis.98% PPV for cirrhosis.Ito K, Mitchell DG, Gabata T, Ito K, Mitchell DG, Gabata T, Hussain SM. Radiology 1999; Hussain SM. Radiology 1999; 211:723211:723--726726

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

Hilar Periportal SpaceHilarHilar PeriportalPeriportal SpaceSpaceNormalNormalNormal

Early CirrhosisEarly CirrhosisEarly Cirrhosis98% of early cirrhosis 98% of early cirrhosis (no nodularity) (no nodularity) vs. 11% of control vs. 11% of control (p<.0001); 91% positive (p<.0001); 91% positive predictive value.predictive value.Ito K, Mitchell DG, Gabata T. Ito K, Mitchell DG, Gabata T. JMRI 2000; 11:136JMRI 2000; 11:136--140.140.

Fatty Liver Fatty Liver -- Iron Overload Iron Overload -- CirrhosisCirrhosis

ConclusionsConclusionsConclusions1. MRI is highly effective for imaging fatty liver, iron overload, and cirrhosis and its complications.

2. Important goals are measurement of iron concentration, and detection of early fibrosis.

1. MRI is highly effective 1. MRI is highly effective for imaging fatty liver, iron for imaging fatty liver, iron overload, and cirrhosis and overload, and cirrhosis and its complications.its complications.

2. Important goals are 2. Important goals are measurement of iron measurement of iron concentration, and detection concentration, and detection of early fibrosis.of early fibrosis.