Contrast media final

WATER SOLUBLE CONTRAST MEDIA: 

WATER SOLUBLE CONTRAST MEDIA By Dr Pragya Singh Moderator Dr Amita Malik

Slide 2: 

Radiographic contrast visible differences between densities on image Radiographic contrast is product of image receptor contrast and subject contrast

Slide 3: 

Subject contrast difference in transmission of x rays through subject determined by size, shape and x ray attenuating characteristics of subject and energy (kVp) of x ray.

Slide 4: 

Image receptor contrast contrast inherent in the film influenced by processing of the film Contrast medium substance used in radiography to increase contrast of image

Types of Contrast Media: 

Types of Contrast Media Positive contrast substance absorbs x rays organ become radiopaque most common media I,Ba

Negative contrast: 

Negative contrast Organs become more radioluscent. X-rays penetrate more easily. Eg: air,CO2

Slide 7: 

CO 2 gas is used as an alternative to ICM in several diagnostic and interventional techniques Non nephrotoxic Highly soluble Less viscous Cheap

Contrast Media: 

Contrast Media Classification (modality) Iodinated contrast agent (radiographs,CT) Barium sulphate Ultrasound contrast agents MRI contrast agents

HISTORY : 

HISTORY In 1896,first angiogram was performed in an amputated hand {HASCHEK and LINDENTHAL}and cadaver kidney{HICKS and ADDISON}. OSBORN noticed opacification of bladder in a patient receiving sodium iodide –First IVU.{But NaI is toxic} MONIZ found Colloidal thorium dioxide{THOROTRAST} – radio-opaque and no acute side effects.

HISTORY : 

HISTORY T horotrast an alpha emitter retained in RES associated with:- Liver sarcoma Hepatoma Cholangiocarcinoma Myeloid leukemia Transitional cell carcinoma Local granuloma formation

Slide 11: 

Intra-vascular iodinated contrast was first used by MOSES SWICK,, using mono-iodinated pyridone-based agents FIRST GENERATION PYRIDONE-BASED AGENTS: SELECTAN NEUTRAL and UROSELECTAN.{more soluble and less toxic} HISTORY

Iodinated Contrast Agents: 

Iodinated Contrast Agents selectan

HISTORY : 

HISTORY SECOND GENERATION PYRIDONE-BASED AGENTS by BINZ and RATH Di-iodinated pyridone-based agents namely: UROSELECTAN-B and DIODONE

HISTORY : 

HISTORY SWICK then suggested iodinated benzene-ring based compounds and developed MONO-IODINATED HIPPURATE.[was toxic} WALLINGFORD developed low toxicity compound by introducing an amide side chain with acetylation in benzene ring..namely ACETRIZOATE….the first ionic monomer.

Iodinated Contrast Agents : 

Iodinated Contrast Agents Intra vascular use Contain iodine (responsible for radio opacity) Contrast agents delivered into extra vascular and extra cellular space(except in the CNS) 90% eliminated by kidneys in 12 hours

WHY IODINE? : 

WHY IODINE? IODINE(atomic wt 127) provides excellent radio-opacity due to Higher atomic no: and K-shell electron binding energy of 34kev which is lower than but closed to mean energy used in diagnostic x-rays and thus maximising the photo-electric effect.

Iodinated Contrast Agents: 

Iodinated Contrast Agents Principal classes of iodinated radiological contrast medium 1 CONVENTIONAL HOCM Ionic monomer 2 LOCM Ionic dimer Non ionic monomer Non ionic dimer

CONVENTIONAL HOCM Ionic monomer: 

CONVENTIONAL HOCM Ionic monomer

Ionic monomer: 

Ionic monomer Acetrizoate (Diaginol, Urokon) Diatrizoate (Angiografin, Hypaque, Renografin, Urografin, Urovison) Iodamide (Uromiro) Ioglicate (Rayvist) Iothalamate (Conray) Ioxithalamate (Telebrix) Metrizoate (Isopaque, Triosil)

Iodinated Contrast Agents: 

Iodinated Contrast Agents IONIC MONOMERS Tri-iodinated benzoic acid derivative with Na+ / meglumine cation High osmolality > 1400 mosm/kg Iodine:particle ratio of 3:2 Meglumine salts higher viscosity at same I conc.

IONIC MONOMER: 

IONIC MONOMER Further classified on basis of % of compound in the solution.eg. 30%, 70%[ UROGRAFFIN 76%] CONRAY 280 means 280mg iodine per ml of solution. Sodium is toxic to endothelium & BBB So avoided in venography and cerebral angiography.

Ionic monomer : 

Ionic monomer Meglumine salts are used for this. Both pure sodium and pure meglumine salts are associated with high risk of ventricular fibrillation so a mixture of sodium and meglumine is used. Special formulations with calcium and magnesium replacing sodium ions also used.

LOCM CONTRAST MEDIA IONIC DIMERS: 

LOCM CONTRAST MEDIA IONIC DIMERS

LOCM Iodinated Contrast Agents: 

Ionic dimer Iocarmic acid by linking 2 molecules of iothalmic acid as DIMER X ( toxic) Monoacid dimeric agents: Two tri-iodinated benzene rings with single carboxyl other replaced by non-ionizing side group Iodine:particle ratio of 6:2 Low osmolality 600 mosm/kg Examples: loxaglate{ HEXABRIX } LOCM Iodinated Contrast Agents

Ionic dimers: 

Ionic dimers Hexabrix is acceptable arteriographic agent with reduced pain but on i.v shows toxicity so not to be used in IVU, DSA and CT.

Iodinated Contrast Agents: 

Iodinated Contrast Agents NON-IONIC MONOMERS Modified tri-iodinated benzoic acid derivative with carboxyl group replaced by D-glucose group do not dissociate and water-solubility due several hydrophilic hydroxyl groups Iodine:particle ratio 3: 1 Low osmolality 500-700 mosm/kg

Non Ionic Monomer: 

Non Ionic Monomer

Non ionic monomers : 

Non ionic monomers Metrizamide (Amipaque)- The first non-ionic contrast agent. Disadvantage of being unstable at high temperature so cannot be autoclaved and has to be prepared as a lyophilised powder.

NON-IONIC MONOMER: 

NON-IONIC MONOMER Iohexol (Omnipaque) Iopamidol (Iopamiro, Isovue, Niopam, Solutrast) Iopentol (Imagopaque) Iopromide (Ultravist) Ioversol (Optiray)

Iodinated Contrast Agents: 

Iodinated Contrast Agents Non ionic dimer Two non-ionic tri-iodinated benzene rings replacing both carboxyl groups with hydrophilic groups. Iodine:particle ratio 6:1 Low osmolality 300 mosm/kg Examples: lotrolan, lodixanol

Non Ionic Dimer: 

Non Ionic Dimer

Iodinated Contrast Agents: 

Iodinated Contrast Agents Iodine : particle ratio = no. of iodine atoms per molecule of CM / no. of osmotically active particles per molecule of CM contrast media iodine particle ratio Ionic monomer 3:2 Ionic dimer 6:2 Non ionic monomer 3:1 Non ionic dimer 6:1

PHYSICAL PROPERTIES OF CONTRAST AGENTS: 

PHYSICAL PROPERTIES OF CONTRAST AGENTS VISCOSITY: measures rate of flow through standard thin capillary tube under standard condition of temperature and pressure. practical:force required to inject. depends on concentration and size of molecule, temperature,inner diameter and length of catheter and no: of catheter holes.

Slide 34: 

Viscosity is inversely propotional to temperature. Viscosity is reduced by warming the solution to body temperature. 2. OSMOLALITY:is the conc.of dissolved particles expressed as mOsm per Kg of H2O.

Slide 35: 

Blood & CSF surrounding brain and spinal cord have osmolality of 290mOsm/Kg. Non-ionic monomers & ionic dimeric even have higher osmolality. Non-ionic dimers are iso-osmolar. Closer the osm. Of RCM to body fluids- better tolerance.

Slide 36: 

Directly responsible for S/E heat and discomfort, BBB damage, renal damage and electrolyte imbalance. Both viscosity and osmolality depends on the conc. Of contrast = strength of RCM as mg/ml. So increasing strength increases opacification power but also increases visc. And osmolality, thereby decreasing tolerance.

Slide 37: 

3. CHEMOTOXICITY : mechanism responsible for causing toxic effects of RCM which cannot be explained by other means(osmol, charge) Hydrophilicity : preference for aqueous solutions. Lipophilicity : preference for lipid solutions. more hydrophilic is less toxic.

Slide 38: 

PARTITION COEFFICIENT :ratio of the amount of CM dissolved in lipid layer to amount dissolved in aqueous layer. Larger the coefficient,more the lipophilicity and more the toxicity. Protein binding : % of RCM which becomes bound to plasma proteins.eg: cholegraphic agents(higher toxicity than urographic RCM)

Slide 39: 

Protein binding esp. enzyme binding AChEsterase inhibition as an indication of toxicity. Na is cardiac, hepatic & renal toxic and peripheral vasodilatation. Meglumine is less toxic but increase viscosity.

RCM kinetics: 

RCM kinetics All the 4 groups have high water solubility and low plasma protein binding. So distributed in extra-cellular space & minor in intra-cellular. Passes through GBM & very small amount is exc. Or reabsorbed in tubules{just like inulin} So RCM can be used to measure GFR.

RCM kinetics: 

RCM kinetics At normal GFR t1/2 is 1.5-2hrs If GFR dec. by 2, t1/2 is doubled. Small amount also excreted via biliary system. HOCM produces larger osmotic diuresis & so have lower urinary conc. than LOCM. BRAIN : does not cross BBB unless breached. RBCs: rigid and deformed.

RCM kinetics: 

RCM kinetics Vascular endothelium damaged – producing thrombus.(more by HOCM) All RCM when mixed with blood in tube/angiographic catheters act as anti-coagulants. LUNGS: on i.v. bolus{IVU,CT,pulm. Angiography} –HOCM increases pulm.arterial pressure, increased RBC rigidity—pulm hypertension.

RCM kinetics: 

RCM kinetics Also causes histamine release from mast cells in lungs..(so S/E like urticaria and vomiting is more after i.v. than intra-arterial) LOCM to be used in pts. With decreased lung functions. HEART:On coronary arteriography HOCM causes larger reduction in contractile force.

RCM kinetics: 

RCM kinetics Ionic CM are chosen those with Na(over meglumine) same as that of plasma – decrease rise of VF. Non-ionic CM used with optimum electrolyte content & oxygen saturation reduces S/E. PERIPHERAL VASCULAR DS.:femoral arteriography CM using 300mg/ml produces osmotoxicity and chemotoxicity.

RCM kinetics: 

RCM kinetics SUB-ARACHANOID SPACE: only non-ionic CM are to be used. HOCM produces chemo and osmotoxicity. KIDNEY: IVU requires high iodine conc.to line cortex,pelvis,ureters. Cortical nephrogram depends on conc.of CM in cortical blood vessel & in primary urine in bowman’s space & proximal tubules.

RCM kinetics: 

RCM kinetics Pyelogram depends only upon the conc. of CM in final urine. Selective renal arteriography: HOCM produces more proteinuria. Renal insufficiency is larger with larger CM doses & lower pre-injecton GFR.

Iodinated Contrast Agents: 

Iodinated Contrast Agents Adverse reactions – Types Acute Idiosyncratic Non – idiosyncratic Delayed

Iodinated Contrast Agents: 

Iodinated Contrast Agents Idiosyncratic reactions : begins with in 20min of inj.and independent of dose given. Not true HSR since Ig E not involved (c/a ANAPHYLACTOID RXNS.) Pathogenesis – proposed causes Release of vasoactive substances. Involvement of coagulative, fibrinolytic,kinin and complement systems

Iodinated Contrast Agents: 

Iodinated Contrast Agents Non-idiosyncratic rxns. :dependent upon dose and specific for substance administered.mechanism: Osmotoxicity Chemotoxicity Ionic charge which effects local elec. balance,nerve conduction Ion toxicity Dose Speed of injection

IDIOSYNCRATIC RXNS.: 

IDIOSYNCRATIC RXNS. MILD Nausea Ltd urticaria Mild pallor Limb pain MODERATE Sev.vomiting Extensive Urticaria Dyspnoea Chest/abdominal pain SEVERE Unconsciousness Pulm.edema Cardiac arrest Arrythmias

Iodinated Contrast Agents: 

Iodinated Contrast Agents Non-Idiosyncratic reactions Manifestations Physiologic effects: hypotension associated with tachycardia due to peripheral vasodilatation. Vasovagal reactions: hypotension associated with bradycardia. Contrast induced renal failure

Slide 52: 

Convulsions Cutaneous- Phlebitis/extravasation Fetal/Neonatal toxicity

Iodinated Contrast Agents: 

Iodinated Contrast Agents Delayed reactions Occur 1 hour to 1 week after CA Manifestations - flu like symptoms - delayed arm pain - rash/ pruritus - salivary gland swelling - Steven Johnson syndrome ,SLE more common with LOCM

Iodinated Contrast Agents : 

Iodinated Contrast Agents Drugs and Equipments Oxygen Adrenaline 1:1000 Antihistamine H1:suitable for injection Atropine β 2 agonist metered dose inhaler I V fluids - normal saline /Ringer solution Anti convulsant drugs (diazepam) Sphygmomanometer One way mouth breather apparatus

Iodinated contrast agents: 

Iodinated contrast agents Nausea/Vomiting Transient : Supportive treatment Severe, protracted : Antiemetic drugs

Iodinated contrast agents: 

Iodinated contrast agents Urticaria Scattered, transient: Supportive treatment Scattered, protracted: H1 antihistamine IM Profound : Adrenaline 1:1,000 :0.1 - 0.3 ml IM

Iodinated contrast agents: 

Iodinated contrast agents Bronchospasm Oxygen by mask (6-10 l/min) Beta 2-agonist inhalation Adrenaline 1:1,000:0.5 ml IM

Iodinated contrast agents: 

Iodinated contrast agents Hypotension Elevate patient’s legs Oxygen by mask (6-10 l/min) Intravenous fluid: rapidly, normal saline or lactated Ringer’s solution If unresponsive:adrenaline:1:1,000, 0.5 ml (0.5 mg) IM, repeat as needed

Iodinated contrast agents: 

Iodinated contrast agents Vagal reaction (hypotension and bradycardia) Elevate patient’s legs Oxygen by mask (6-10 l/min) Atropine 0.6-1.0 mg IV. Intravenous fluids: rapidly, normal saline or lactated Ringer’s

ACUTE RENAL FAILURE: 

ACUTE RENAL FAILURE Aggressive fluids Lasix Dopamine Mannitol

PULMONARY EDEMA: 

PULMONARY EDEMA Occurs if iodinated(esp. ionic) CM is aspirated into lungs. Treatment: Oxygen Lasix Steroids

Iodinated contrast agents: 

Iodinated contrast agents Cardiac arrest Call for cardiac team Ask for emergency drugs/ Defibrillator CPR - Airway - Breathing - Circulation

Iodinated contrast agents: 

Iodinated contrast agents Seizures Turn lateral Midazolam 1-2mg/ Diazepam 5mg IV O2

Ionic vs. Non-ionic CM: 

Ionic vs. Non-ionic CM Overall reactions(%) Severe reactions(%) Ionic CM Non ionic CM Ionic CM Non ionic CM Katayama et al(1990) 12.7 3.1 0.22 0.04 Palmer(1988) 3.8 1.2 0.1 0.01 Wolf et al(1989) 4.1 0.7 0.4 0.0

Advantages of non-ionic over ionic: 

Advantages of non-ionic over ionic Reduced tonicity Myelography – LOCM >> HOCM Chemotoxicity: LOCM more hydrophilic due to longer side chains, sheilds I atoms, no Na ions,dec. damage to BBB. Inc.hydrophilia=less tendency to cross cell membranes Decreased HSR rxns

DOSAGE OF ADRENALINE: 

DOSAGE OF ADRENALINE i.m. is first choice route used in conc. Of 1:1000. <6 months 0.05 ml 6mnths – 6yrs 0.12ml 6 – 12 yrs 0.25ml adults 0.5ml

i.v. epinephrine: 

i.v. epinephrine Severely ill pts, when circulation is slow and absorption from i.m. site is slow. Slow i.v.-dose of 500micrograms( 5 ml of 1:10,000)@ 1 ml/min. stopping when response occurs. Children – 10micrograms(0.1 ml/kg)

Slide 68: 

FACTORS PREDISPOSING TO REACTIONS 1PREVIOUS ADV REACTION 2 H/O ALLERGY/ATOPY 3 H/O ASTHMA 4 CARDIAC DISEASE 5 PRESENCE OF DEHYDRATION 6 HAEMATOLOGICAL,METABOLIC CONDITION LIKE SICKLE CELL ANAEMIA, MULTIPLE MYELOMA,PARAPROTEINAEMIA 7 RENAL DISEASE

Slide 69: 

In pts with high risk of acute rxns to CM: Re-evaluate the indication and use alternatives. LOCM>>HOCM If previous rxn. was : Mild: can be performed without pre-medication Moderate: pre-medication required.

Slide 70: 

Severe: pre-medication + investigation under anaesthesiologist. PRE-MEDICATION: ELECTIVE investigation: PREDNISOLONE 50mg orally 12hrs and 2 hrs before the investigation. CLEMASTINE 1mg/ml i.m 1 hr before.

Slide 71: 

EMERGENCY investigation: HYDROCORTISONE 200mg i.v. immediately & then every 4 th hr until investigation is complete. CLEMASTINE 1mg/ml i.m. 1 hr before investigation.

CONTRAST INDUCED NEPHROPATHY : 

CONTRAST INDUCED NEPHROPATHY impairment in renal function (an increase in serum creatinine level by >25% or 0.5mg/dl) within 3 days of intravascular injection with contrast media absence of an alternative etiology

CIN: 

CIN Risk factors Raised s-creatinine levels, particularly secondary to diabetic nephropathy. Dehydration Congestive heart failure Age over 70 years old Concurrent administration of nephrotoxic drugs, e.g. aminoglycosides ,NSAIDS

In pts with risk factors:: 

In pts with risk factors: DO’s: HYDRATION: atleast 100ml/hr orally or i.v. 4hrs before to 24hrs after adm. Use LOCM Stop nephrotoxic drugs atleast 24hrs before. Consider alternative imaging.

Slide 75: 

DONT’s: HOCM Large doses Mannitol or diuretics (esp. loop) Multiple studies in a short period of time.

TREATMENT OF CIN: 

TREATMENT OF CIN Volume expansion: most important N- acetyl cysteine : free radical scavenger in dose of 1200mg in two divided doses or 150 mg/kg i.v.

Iodinated Contrast Media: 

Iodinated Contrast Media Absolute contraindication: patient with manifest hyperthyroidism Radioactive iodine treatment: Patient not to receive ICM for 2 months Isotope imaging thyroid Patient not to receive ICM for 2 months

PRECAUTIONS FOR USE: 

PRECAUTIONS FOR USE HYDRATION: any water and electrolyte imbalance should be corrected & esp. in MM, DM,polyuria,oliguria,hyperuricemia, babies and elderly. PRE-MEDICATION: in pheochromocytoma pts. prior alpha receptor blockers. ANXIETY: inc. chances of rxns.should be sedated.

Slide 79: 

4.CO-MEDICATION: neuroleptics and anti-depressants should be discontinued 48hrs before to 24hrs post procedure.Since they decrease seizure threshold. 5.COAGULATION, FLUSHING OF CATHETERS: non-ionic media have less anti-coagulant properties so they should not be allowed to remain in contact with blood and syringe or i.v. catheters

Slide 80: 

which should be flushed frequently to minimise risk of clotting which may rarely lead to thrombo-embolic episodes. 6. OBSERVATION: of pt. after injection of contrast for atleast 30 min. 7. PRE-TESTING: not recommended. 8. STORAGE: protect from light and out of reach of ionising radiations.

Slide 81: 

8. SINGLE USE: vials are not for withdrawal of multiple doses. CM should not be drawn into syringe until immediately before use. Solutions not used in one session must be discarded. 9. MIXING: CM should not be mixed with other drugs.

INTERACTIONS: 

INTERACTIONS Thyroid function tests: following CM administration, capacity of thyroid tissue to take up radio-isotopes for diagnosis is reduced for upto 2 wks. Lab tests: high doses of CM in blood and urine may interfere with lab test results of bilirubin,proteins or inorganic substances.

Slide 83: 

3. Oral cholecystographic agents: no e/o interactions with renally excreted CM. 4. CM and Metformin: risk of lactic acidosis in pts. with DM II S. creatinine measured in every pts. LOCM used always.

RCM AND METFORMIN: 

RCM AND METFORMIN ELECTIVE INVESTIGATION: * S. creatinine normal : investigation done with metformin stopped at the time of study & not resumed for 48hrs. Restarted only if S. creatinine normal. * S. creatinine abnormal : metformin stopped 48hrs before & restarted only if S. cratinine is normal.

Slide 85: 

EMERGENCY INVESTIGATION: * S.creatinine normal: as elective * S.creatinine abnormal : weigh risk and benefits. Consider alternative imaging. Metformin stopped Hydration given Monitor renal functions.

Slide 86: 

Look for the signs of lactic acidosis: Vomiting, nausea, epigastric pain, lethargy, somnolence, diarrhoea, thirst. Blood : pH < 7.25 Lactic acid >5 mmol

RCM & SPECIAL CONDITIONS: 

RCM & SPECIAL CONDITIONS Neonates, infants &childrens: pre-disposed to electrolyte imbalance. Care should be taken about dosage. Pregnant women: no e/o teratogenicity Breastfeeding women: very small amount is excreted in milk. No e/o adv. effect on baby. Elderly: risk of MI, arrythmias & extra-systoles, ARF. Dosage is important.

APPLICATIONS: 

APPLICATIONS 1 RENAL TRACT IMAGING ( IVP, RGP, MCU, RGU) 2 CEREBRAL ANGIOGRAPHY 3 MYELOGRAPHY-NON IONIC MEDIA USED ,IONIC VERY TOXIC IN SUBARACHNOID SPACE. EARLIER MYODIL USED –CHRONIC ADHESIVE ARACHNOIDITIS(ABANDONED)

Slide 89: 

4. CARDOVASCULAR IMAGING 5. PERIPHERAL ANGIO-LOCM PREFERRED I-300mg/ml 6. PULM ANGIO-LOCM PREFFERED CAUSE LESS ELEVATION OF PULM ARTERY PRESSURE 7. CORONARY ANGIO-LOCM USED 8. HYSTERO-SALPINGOGRAPHY

DOSAGE : 

DOSAGE as per RCM with I content of 300mg/ml. IVU Adults: 50-150ml Neonates: 3-4.8ml/kg <1yr: 2.5-4ml/kg >1yr: 1-2.5ml/kg CT Brain CT Body 50-200ml 100-200ml

Slide 91: 

Intra-venous DSA 100 – 250 ml HSG upto 35ml Fistulography upto 100ml RGP 10 to 20ml

Slide 92: 

Sialography 1 – 3 ml ERCP upto 100ml Retrograde cholangiography upto 60 ml

Barium sulfate: 

Barium sulfate Barium sulfate is present in earth crust due to toxic impurities barium sulfate commercially manufactured by precipitation from other compounds white crystalline powder molecular weight 233 specific gravity 4.5

Barium sulfate: 

Barium sulfate Particle size: Larger particles commercial “high density” products. double contrast gastric studies contain particles 18 micron or larger single contrast studies homogenous particle size

Barium sulfate: 

Barium sulfate Flocculation : chemical process results in coarse precipitate of barium particles. protective agents, flocculation has ceased to be a major problem. Viscosity: barium sulfate products exhibit non Newtonian flow, viscosity varies with flow rate . Viscosity determines flow rate and mucosal coating.

Barium sulfate: 

Barium sulfate Additives: . stabilizing, flavoring, coating and viscosity varying agents. Although barium sulfate does not support bacterial growth, some additives are organic products. suspension should be refrigerated if it is to be kept overnight.

Barium sulfate: 

Barium sulfate Measuring systems : Specific gravity is the ratio of suspension mass to mass of equal amount of water. weight to volume (W/V) certain weight of barium sulfate added to enough water to obtain predetermined volume, weight to weight (W/W) certain weight of barium sulfate added to enough water to obtain a predetermined total weight.

Barium sulfate: 

Barium sulfate Barium preparations High density ( >200 % W/V) Medium density (100 – 200% W/V) Low density (50 – 100 % W/V)

Barium sulfate: 

Barium sulfate esophagus : 100% W/V suspension stomach : wide range particle size, 240% W/V small bowel : FT - density <40% W/V. enteroclysis - higher density ~100%W/V Colon: double contrast -density 80 to 120% W/V single contrast - density ~50%w/v

Barium sulfate: 

Barium sulfate Barium sulfate is safe contrast agent. Complications leakage into the pleural or peritoneal spaces leakage into the mediastinum possible pulmonary aspiration

Ultrasound contrast agents: 

Ultrasound contrast agents Ultrasound imaging and Doppler are based on scattering of sound energy by interfaces of material with different acoustic properties Amplitude of echo generates ultrasound images Frequency shifts in the backscattered echo provide information about moving targets.

Ultrasound contrast agents: 

Ultrasound contrast agents Requirements : easily introducible into the vascular system be stable for duration of diagnostic procedure No toxicity modify acoustic properties of tissues

Ultrasound contrast agents: 

Ultrasound contrast agents Administered – Intravenous Injection Removed – Dissolve in circulation – Filtered by liver – Cleared ~ 15 minutes

Ultrasound contrast agents: 

Ultrasound contrast agents Free gas bubbles . Gramiak and Shah (1968). injected saline into aorta during echocardiographic recording and noted echoes within the normally echo free lumen limitation bubbles are large effectively filtered by lungs and unstable go back into solution. Except by direct injection, unsuitable for imaging left sided cardiac chambers, coronary circulation and systemic arteries

Ultrasound contrast agents: 

Ultrasound contrast agents Encapsulated air bubbles. encapsulate gas within shell create stable particle encapsulated microbubble of red blood cell size survive passage through heart and pulmonary capillary network Feinstein produced microbubbles sonication of human serum albumin solution. (Albunex)

Ultrasound contrast agents: 

Ultrasound contrast agents Low solubility gas bubbles: shells allow air to diffuse in solution. effective duration just few minutes. Newer agents use low solubility gases lower diffusion rate increase agent life in blood.

Ultrasound contrast agents: 

Ultrasound contrast agents Selective uptake agents: . Agents are capable of providing ultrasound contrast during their metabolism and while in blood pool. Colloidal suspensions of liquids -perflurocarbons and agents with durable shells are taken up by the RES from where they are ultimately excreted. Levovist provides late phase enhancement in liver and spleen after being cleared from vascular system.

Ultrasound contrast agents: 

Ultrasound contrast agents Microbubble Gas Stabilization FIRST GENERATION Agitated saline Air None Echovist Air None SECOND GENERATION Levovist Air Palmitic acid Albunex Air Sonicated albumin THIRD GENERATION Optison Perfluoropropane Sonicated albumin Echogen Dodecafluoropentane Surfactant Sonovue Sulphur hexafluoride Phospholipids PESDA Perfluorobutane Sonicated albumin LIVER SPECIFIC AGENTS Levovist Air Palmitic acid

Ultrasound contrast agents: 

Ultrasound contrast agents Optison is perfluropropane filled albumin shell. Sonovue is sulphur hexafluorane in phospholipids shell. Definity comprises a perfluoropropane microbubble coated with a particularly flexible bilipid shell

Ultrasound contrast agents: 

Ultrasound contrast agents Levovist dry mixture 99.9% galactose micro particles 0.1% palmitic acid. dissolution and agitation in sterile water galactose disaggregates into micro particles providing irregular surface for adherence of microbubbles 3 to 4 micron in size palmitic acid coating stabilizes microbubbles

Ultrasound contrast agents: 

Ultrasound contrast agents

Ultrasound contrast agents: 

Ultrasound contrast agents Microbubble behavior: Microbubble scatter ultrasound dependent on amplitude of transmitted sound. At low incident pressure microbubbles produce linear backscatter enhancement increase echo from blood. At higher incident pressure(50 to 100 kPa ) back scatter show non linear characteristics-emission of harmonics . As the peak pressure reaches nearer 100 kPa agents exhibit transient non linear scattering resulting in destruction.

Ultrasound contrast agents: 

Ultrasound contrast agents Clinical Applications of Ultrasound Contrast LVO – Left Ventricular Opacification Liver tumor detection and characterization Myocardial perfusion Kidney (transplants), breast, prostate, etc. Stroke Research for targeted/molecular imaging – Combined with drug delivery Therapy guidance – RFA – Biopsy

MRI contrast agents: 

MRI contrast agents

MRI contrast agents: 

MRI contrast agents No spin, no contrast Spin density is the most fundamental of contrast in MRI Spin density is related to water content of the tissue

MRI contrast agents: 

To enhance the signal from spin density: Gastrointestinal imaging - Drinking water Lung imaging - Inhaling hyperpolarized inert gas He MRI contrast agents

MRI contrast agents: 

The shorter the repetition time (TR) the greater the T1 contrast. The longer the echo time (TE) the greater the T2 contrast. MR contrast agents act to change the relaxation times of the substrate where they localize MRI contrast agents

MRI contrast agents: 

MRI contrast agents T1 agents: predominant effect T1 relaxation → ↑ signal intensity (positive contrast agents) e.g. paramagnetic contrast agents T2 agents: predominant effect T2 relaxation → ↓signal intensity (negative contrast agents) e.g. superparamagnetic contrast agents

Paramagnetic CA : 

Contain ion with large number of unpaired electrons This gives it larger magnetic moment than the proton enhances the local magnetic fields that fluctuate in the vicinity of a proton Paramagnetic CA

MRI contrast agents: 

MRI contrast agents Many transition metals and lanthanide metals with unpaired spins effective relaxation agent: local magnetic field fluctuation match protons Larmor frequency seen in Fe3+, Mn2+ and Gd3+

Gadolinium chelates: 

paramagnetic ions eg. Gadolinium By themselves these ions are highly toxic so bound up in large molecules eg. DTPA They tend not to permeate the blood brain barrier and so enhance tumors that lack the barrier Gadolinium chelates

MRI contrast agents: 

MRI contrast agents Gd-DTPA is a linear ionic Gd-chelate Gd-DOTA is a cyclic ionic chelate. Gd-DTPA-BMA (Omniscan) is nonionic linear chelate Gd-HP-D03A (Prohance) is non ionic cyclic chelate

MRI contrast agents: 

MRI contrast agents

MRI contrast agents: 

MRI contrast agents Gadopentetate Dimeglumine (Magnevist®), Gd-DTPA ( 1981), first paramagnetic MRI CA (ionic) Gd3+ toxic, bound DTPA chelate stable complex. intravenous administration→ distributed extracellular space → eliminated unchanged kidneys.

MRI contrast agents : 

MRI contrast agents Gadoteridol (ProHance®) Gd-HP-DO3A nonionic cyclic chelate MRI CA with low MW complex of gadolinium It highlights areas of increased vascularity After intravenous injection, most of dose is excreted unchanged within 24 hours.

MRI contrast agents : 

MRI contrast agents Gd-DTPA-BMA Omniscan® nonionic chelate complex low osmolality paramagnetic MRI contrast agent. efficacy similar to Gd-DTPA. i.v. Enhance cranial and spinal lesions BBB

MRI contrast agents : 

MRI contrast agents

MRI contrast agents: 

MRI contrast agents Hepatobiliary agents: substantial hepatic uptake and biliary excretion T1 enhancement

MRI contrast agents: 

MRI contrast agents signal of healthy liver tissue ↑ T1 weighted sequences, but not in liver lesions.

MRI contrast agents: 

MRI contrast agents Hepatobiliary MRI agents : MultiHance® (Gadobenate Dimeglumine) Gd - BOPTA Primovist™(Gd -EOB – DTPA ) Teslascan® (Mn DPDP) Gd-HIDA Cr-HIDA Fe-EHPG IronIII

MRI contrast agents : 

MRI contrast agents

MRI contrast agents: 

MRI contrast agents MultiHance ® NAME OF COMPOUND Gadobenate dimeglumine, Gd-BOPTA CENTRAL MOIETY Gd2+ CONTRAST EFFECT T1, Predominantly positive enhancement PHARMACOKINETIC Extracellular, hepatobiliary CONCENTRATION 334 mg/ml DOSAGE 0.05 mmol/kg for Liver MRI 0.1 mmol/kg for CNS MRI INDICATION CNS, Liver MRI

MRI contrast agents: 

MRI contrast agents Teslascan ® NAME OF COMPOUND Mangafodipir trisodium, Manganese dipyroxyl diphosphate, MN-DPDP CENTRAL MOIETY Mn2+ CONTRAST EFFECT T1, Predominantly positive enhancement PHARMACOKINETIC Hepatobiliary, pancreatic, adrenal CONCENTRATION 0.01 mmol/L DOSAGE 5 µ mol/kg, 0.5 ml/kg INDICATION Liver lesions

MRI contrast agents: 

MRI contrast agents Another liver contrast agent is targeted RES targeted CA phagocytosed by RES cells superparamagnetic iron oxide accumulate in RES of the liver →darken healthy liver tissue in T2 weighted images.

MRI contrast agents: 

MRI contrast agents (SPIO) superparamagnetic iron oxide- colloids microcrystalline magnetite cores coated with dextrans (in ferumoxide) or siloxanes (in ferumoxsil). T2 agents taken by RES cells tissue specific contrast agents Feridex®, Endorem™, GastroMARK®, Lumirem®, Sinerem®, Resovist®

MRI contrast agents : 

MRI contrast agents (USPIO) ultra small superparamagnetic iron oxide (median diameter less than 50nm) are used as MRI CA (Sinerem®, Combidex®, Clariscan™) differentiate metastatic from inflammatory lymph nodes. angiogenesis in malignant tumors Longer plasma life than SPIO

MRI contrast agents: 

MRI contrast agents Hepatobiliary CA vs. Targeted RES CA: More hepatocytes than Kupffer cells improved uptake effectiveness of Hepatobiliary CA Hepatobiliary CA better opacification of biliary ducts and gallbladder due to biliary excretion. Hepatobiliary CA are fast excreted. RES targeted CA remain longer ↑ possible side effects.

MRI contrast agents: 

MRI contrast agents Blood pool agents prolonged investigation time Macromolecular Gd-chelates (Albumin-Gd-DTPA, Dextran-GdDTPA, Polylysin-Gd-DTPA) paramagnetic liposomes USPIO

MRI contrast agents: 

MRI contrast agents Oral contrast agents no absorption by stomach or intestines complete excretion no motion or susceptibility artifacts affordability uniform marking of the gastrointestinal tract.

MRI contrast agents: 

MRI contrast agents positive oral contrast agents improve separation of bowel loops, detection of polyps in colon assessment of inflammatory bowel in small intestine. positive oral contrast agents are gadolinium solution, ferric ammonium citrate, different oil emulsions. signal of positive contrast medium may decrease caused by dilution in GI secretions. similar signal as bright masses, which make (e.g. lipoma) detection difficult.

MRI contrast agents: 

MRI contrast agents Negative oral contrast media superparamagnetic particles induce local field inhomogeneities, shortening T1 and T2 predominant T2-weighted effects. Benefits: reduction of ghosting artifacts caused by lack of signal Disadvantages: High cost, generate susceptibility artifacts (gradient echo sequences) poor availability, and limited evaluation of side effects

MRI contrast agents: 

MRI contrast agents Negative Oral Contrast Agents Categories of negative oral contrast agents: Gastrointestinal diamagnetic contrast agent Gastrointestinal superparamagnetic contrast agents Perfluorochemicals Blueberry juice,pineapple juice (MRCP)

MRI contrast agents: 

MRI contrast agents GI MRI Diamagnetic CA Diamagnetism -induction of negative magnetic susceptibility within externally applied magnetic field. Suspension of clay minerals (Kaopectate with kaolin) –signal absence in stomach and duodenum. Barium sulfate- diamagnetic properties of Ba particles and replacement of water protons with Ba -signal loss

MRI contrast agents: 

MRI contrast agents GI MRI superparamagnetic CA : Superparamagnetic iron oxide Magnetite albumin micro sphere T2 (negative) CA Disadvantages are susceptibility artifacts

MRI contrast agents : 

MRI contrast agents Ferrioxamines: potential iron oxide–based paramagnetic agent I.V. MRI CA . Ferrioxamine methanesulfonate -genitourinary system imaging Hydroxyethyl-starch-ferrioxamine -myocardial vascular flow Ferrioxamine-B - hepatobiliary CA

MRI contrast agents: 

MRI contrast agents Side effects Nausea, vomiting urticaria ,rash generalized anaphylactoid reactions back pain may occur with SPIO

Slide 147: 

NEPHROGENIC SYSTEMIC FIBROSIS OCCUR IN PATIENTS WITH ADVANCE RENAL IMPAIRMENT OR ON DIALYSIS CHARECTERISED BY SCLERODERMA LIKE SKIN CHANGES. OTHER ORGANS LIKE HEART,LIVER AND LUNG CAN BE AFFECTED MORE WITH LINEAR AND NON IONIC Gd compound

Recent advances: 

Recent advances Gadolinium in CT: X-ray absorption coefficient is superior to iodine, especially at higher CT energies. drawback : high osmolality

Recent advances: 

Recent advances Combining high X-ray-absorbing characteristics of iodinated agents with beneficial attributes of MR agents : hybrids between classical CT and MR agents. molecules with three iodine atoms and three lanthanides Targeted USCA-outfitted with ligand that bind to specific receptors expressed by cells of interest Nanodiamond agents 15times more sensitive in MRI

Recent advances: 

Recent advances

Slide 151: 

THANK YOU