Nuclear imaging in  kidney disease
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Nuclear imaging in kidney disease

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  • —2-year-old girl with fever. Dimercaptosuccinic acid (DMSA) renal cortical scintigraphy scan obtained same day as ultrasound (C) shows corresponding photopenic defect (arrow). Follow-up DMSA scan obtained 8 months later (D) shows resolution of defect, consistent with recovered pyelonephritis. <br />

Nuclear imaging in  kidney disease Nuclear imaging in kidney disease Presentation Transcript

  • USE OF NUCLEAR IMAGING IN KIDNEY DISEASES : INDICATIONS AND INTERPRETATIONS 20-5-13
  • Isotopes     Any given element may have many isotopes All isotopes of a given element have the same no of protons and differ only in the no of neutrons Some of these isotopes have unstable nuclear configuration and seek greater stability by decay/disintegration to a more stable form Isotopes attempting to reach stability by emitting radiation are called radionuclides/radioisotopes
  • Radionuclides    Photon Emitting(imaging) – Tc99m; Mo99;I123;Ga67;In113;Kr81;Th201 Positron Emitting(imaging) C11;N13;O15;F18;Rb82 Used for therapy- P32;Sr89;Y90;I131;Sm153
  • Radionuclides for Imaging Desirable characteristics Minimum particulate emission Primary photon energy between 50-500 keV Physical T1/2 > time reqd to prepare material Effective T1/2 longer than examination time Low toxicity Stability or near stability of the product 
  • Technetium 99m      Fulfills many criteria of ideal radionuclide No particulate emission 6 hour half life A predominant (98%) 148KeV photon conversion Used in > 70% of nuclear imaging procedures in United States
  •  Nuclear medicine is a branch of  medicine  and imaging that uses radionuclides and relies on the process of radioactive decay in the diagnosis and treatment of disease.  Used in Nephro-Urology since 1960s
  •  Functional and anatomic information  More organ / tissue specific c/t whole body scans  RADIOPHARMACEUTICALS = RADIONUCLIDES + PHARMACEUTICAL
  • NUCLEAR SCINTIGRAPHY TECHNIQUES  2D Scintigraphy  - use of internal radionuclides to create twodimensional images.  3D  SPECT - tomographic technique using gamma camera data from many projections and reconstructed in different planes  HYBRID SCAN - SPECT/CT and PET/CT
  • TOPICS  Renal Scintigraphy  ACEI renal scan  Renal Transplant Scintigraphy  Radionuclide cystogram
  • Renal scintigraphy INDICATIONS        Renal perfusion and function Urinary Tract Obstruction (Furosemide renal scan) Reno-vascular HTN (Captopril renal scan) Infection (renal morphology scan) Pre-surgical quantitation (nephrectomy) Renal transplantation Congenital anomalies/masses(renal morphology scan)
  • Radiopharmaceutical Agents 1. Grouped into three categories: Those excreted by glomerular filtration, 1. Those excreted by tubular secretion, and 2. Those retained in the renal tubules for long periods
  • Radiopharmaceutical Agents Glomerular Agents  Tc 99m DTPA Cr-EDTA 51 I 125 Iothalamate
  • Glomerular Filtrating Agents Tc-99m DTPA (Diethylenetriamine pentaacetic acid) COOH COOH N HOOC N N COOH COOH
  • Tc 99m DTPA • • • Inulin clearance remains the gold standard to measure GFR, but it is expensive, time consuming, and requires a steady-state plasma concentration and accurate and timed urine collection 99m Tc-DTPA is recommended agent is for GFR measurement. 5- 10% plasma protein binding, so it tends to underestimate the GFR(insignificant)
  • • • • • Peak renal activity after 3 – 4 min. 90 % filtered within 4 hours. The extraction fraction of 99mTc-DTPA is approximately 20 per cent; for this reason, not useful for imaging , in patients with impaired renal function. In such cases, agents with higher extraction efficiencies such as 99mTc-MAG3 more appropriate.
  •  51Cr-EDTA, which may provide more accurate values for GFR, but cannot be used for imaging.
  • Tubular secreting agents:    I131/I123 OIH Tc99m MAG3 Tc99m EC Proximal convoluted tubules
  •   p-Aminohippuric acid (PAH) is the gold standard for the measurement of ERPF. However, it is not well suited for routine studies.
  • I-131/I-123 Orthoiodohippurate O -C-NH-CH2-COOH I Chemical structure similar to the Paraaminohippuric acid
  • I-131 OIH Secreted by tubules – 80% & glomerular filtration - 20% Chemically & pharmacokinetically similar to PAH Plasma protein binding – 70% Cortical peak time = 3-5 min Radiation absorbed dose to bladder= 0.74 rad/mCi
  •   The main disadvantages of 131I-OIH are the suboptimal imaging characteristics of 131I. 123 I-OIH has better imaging qualities, but 123I is more expensive and less available.
  • Tc99m MAG3 (Mercaptoacetyl triglycine) CH2-COO S O N Tc O N N O
  • Tc99m MAG3       70 – 90 % PROTEIN BINDING 89% TUBULAR SECRETION 11% GLOMERULAR FILTRATION Extraction fraction of 40-50%. Provides a high target-to-background ratio, good image quality, and more accurate numerical values, particularly when the kidney function is low or immature 5 TO 10 mCi i.v. ( ADULTS)
  • Tc99m L,L-EC (Ethylene dicysteine) N N -ooc cooTc S S Exists in 4 different forms D,D-EC; L,L-EC; D,L-EC & L,D-EC
  • EC:      Metabolite of the L,L-ECD(ethylene cystine dimer) with cortical uptake Secretion in proximal convoluted tubules Plasma protein binding is 50% Exact excretion mechanism is not known Clearance is 69-85% of OIH
  • Cortical Binding Agents:  Tc99m DMSA  Tc99m GHA
  • Tc-99m DMSA (Dimercaptosuccinic Acid) H HS COOH HS COOH H
  • Cortical agents Tc99m DMSAPYELONEPHRITIS, INFARCTS, SCARS, ANOMALIES         75% protien binding in 6 hrs 5- 20 % excretion 2 hrs 37% excretion in 24 hrs 40-50% cortical localisation Maximum activity at 3-6 hrs 2 TO 5 mCi i.v. Images at 2 – 4 hrs
  •  Importantly, acute infection can produce abnormalities in the scan; and if the test is being performed to evaluate for cortical scarring, it should be done at least 3 months after an acute infection ( Rosenberg et al, 1992 ).
  • Tc 99m GHA (Glucoheptonate) O O O C O Tc CH O (CHOH)4 CH2OH O C O CH (CHOH)4 CH2OH
  • CONTD..        Tc 99m GH It is both filtered by the glomerulus and bound by the tubules. Glomerular filtration 80-90% Tubular secretion 10-20% 25-40% in 1 hr & 70% in 24 hrs in urine 15% bound to PCT EARLY DYNAMIC FUNCTIONAL imaging DELAYED CORTICAL imaging 10-15 mCi
  • Choosing Renal Radiotracers Clin. Question Perfusion Morphology Obstruction GFR quantitation ERPF quantitation Agent MAG3, DTPA, GHA DMSA, GHA MAG3, DTPA, OIH I-125 iothalamate, Cr-51 EDTA, DTPA MAG3, OIH
  • Basic Renal Scan Procedure
  • Basic Renal Scintigraphy Patient Preparation  Patient must be well hydrated Give 5-10 ml/kg water (2-4 cups) 30-60 min. pre-injection  Can measure U - specific gravity (<1.015)    Void before injection Void @ end of study Int’l Consens. Comm. Semin NM ‘99:146-159
  • Basic Renal Scintigraphy Acquisition  Supine position preferred  Flow (angiogram) : 2-3 sec / fr x 1 min  Dynamic: 15-30 sec / frame x 20-30 min (display @ 1-3 min/frame)
  • Basic Renal Scintigraphy Acquisition (cont’d)  Obtain a 30-60 sec. image over injection site @ end of study   if infiltration >0.5% dose do not report clearance Obtain post-void supine image of kidneys @ end of study Taylor, SeminNM 4/99:102-127
  • International Consensus Committee Recommendations for Basic Renogram  Tracer: MAG3, (DTPA)   Dose: 2 - 5 mCi adult, minimum 0.5 mCi peds Pt. position: supine (motion, depth issues)  Include bladder, heart  Collimator: LEAP  Image over injection site Int’l Consens. Comm. Semin NM ‘99:146-159
  • Radionuclide Renal Evaluation     Functional Imaging(visual assessment of perfusion and function) Renography (time activity curve representative of renal function) Quantification of renal function(GFR & ERPF) Anatomic imaging( cortical imaging)
  • Functional Imaging      Perfusion imaging – Evaluation of renal blood flow and function of native kidneys – posterior projection ; transplanted kidneys – anterior projection 10-20mCi of radiopharmaceutical injected iv in antecubital vein. Imaging renal perfusion is usually begun as soon as bolus is seen in abd. Aorta Subsequent images are taken every 1-5 secs
  •  In normal renal blood flow By 3 sec aorta is fully visualized. By 5-6 sec, both kidneys are seen. Maximal kidney activity is reached in 30-60 sec.
  • DTPA normal
  • Renal functional imaging    At the end of perfusion sequence , imaging for function begins. Dynamic or sequential static; 3-5 min Tc99m DTPA or MAG3 are then obtained over 20-30 mins. Evaluation is similar to an IVP with – anatomy, position, symmetry and adequacy of function & collecting system patency.
  •  With Tc99m MAG3 maximal parenchymal activity is seen at 3-5 min  Activity in collecting system and bladder by 4-8 mins.
  • DTPA normal
  • Renography  A Time Activity Curve  Graphic representation of uptake and excretion of radiopharmaceutical  Information is displayed from time of injection to abt 20-30 mins
  • Renogram Phases  FLOW / VASCULAR PHASE  ( 30 MIN ) (RADIONUCLETIDE ANGIOGRAM) • • FUNCTIONAL PHASE II. Parenchymal phase(uptake) Last for 30-60 sec. • Max activity 3to 5 min Max activity 4-6 secs • UPTAKE AT 2 TO 3 MIN FOR after peak aortic activity SPLIT FUNCTION III. Washout (excretory) phase no activity after 30 min
  • RENOGRAM PHASES
  • Data obtained from renogram  Time to peak cortical activity- 3-5 min  Half-time excretion- time for half of peak activity to be cleared from kidney. N – 8-12 mins  Cortical activity at 20 min/ peak activity : < 0.30 on MAG3 renogram.
  • RELATIVE/SPLIT FUNCTION  Contribution of each kidney to the total function % Lt kid = net cts in Lt ROI --------------------------------------- x 100% net cts Lt + net cts Rt ROI ROI: Region of interest Normal Borderline Abnormal 50/50 - 56/44 57/43 - 59/41 > 60/40 Taylor, SeminNM Apr 99
  • Relative (split) function ROI’s
  • Quantitation of Renal Function GFR & ERPF measurement  Two methods : Plasma sample based clearances :  The amt of activity remaining in blood at prefixed times is a measurement of activity not yet cleared – indirect measure of activity already cleared.  More accurate ,but requires determination of pharmaceuticals levels in plasma and some times in urine. 
  •    Camera based clearances : Counts are obtained from syringe before inj. & subsequently over kidneys after injection. No blood and urine collection. Sufficiently reliable method.
  • Anatomic(Cortical) Imaging (Tc99m DMSA or GH )    Images obtained after 2 to 4 hrs of injection Posterior/ right post. Oblique/ left post. Oblique NORMAL FINDINGS Smooth contour with Homogeneous activity Less uptake in medulla No activity in PCS
  • Diuretic (Furosemide) Renal Scan  Obstructive uropathy (hydronephrosis, hydroureter) may lead to obstructive nephropathy (loss of renal function) Indications:  Evaluate functional significance of hydronephrosis  Determine need for surgery    obstructive hydronephrosis - surgical Rx non-obstructive hydronephrosis - medical Rx/ follow up Monitor effect of therapy
  • PRINCIPLE  Hydronephrosis - tracer pooling in dilated renal pelvis  Furesemide induces increased urine flow  If obstructed >>> will not wash out  If dilated, non-obstructed >>> will wash out  Can quantitate rate of washout (T1/2)
  • PROTOCOL      Oral hydration prior to study NS @ 15ml/kg over 30 min 15 min prior to injection & continued in study @ 200ml/kg/24 hr Bladder catheterization is required in children Tc 99m MAG3 – agent of choice in children with limited function high target-to-background ratio, good image quality, and more accurate numerical values
  • PROTOCOL      Pre requisite – residual function to respond Diuretic given ( infants- 1mg/kg, children 0.5 mg/kg, 40 mg adults ) 20-30 min after radiotracer injection Imaging for 20 – 30 minutes, post micturition image Functional images, renogram time/activity curve( before & after ), wash out half time calculated symmetric uptake and good washout is by definition not obstructed
  • Diuretic Renal Scan Washout (diuretic response) T1/2 time required for 50% tracer to leave the dilated unit i.e. time required for activity to fall to 50% of peak
  • T1/2     Normal < 10 min Obstructed > 20 min Indeterminate 10 - 20 min Best to obtain own normals for each institution, depending on protocol used
  • Scintigraphic evaluation of Hydronephrosis Showing non-obstructive hydronephrosis of the left kidney, The arrow indicating a brisk response to intravenous diuretic.
  • Scintigraphic evaluation of Hydronephrosis Showing obstructive hydronephrosis of the right kidney, The arrow indicating a no response to intravenous diuretic.
  • “F minus 15” Diuretic Renogram  Furosemide (Lasix) injected 15 min before radiopharmaceutical  Rationale: kidney in maximal diuresis, under maximal stress  Some equivocals will become clearly positive, some clearly negative English, Br JUrol 1987:10-14 Upsdell, Br JUrol 1992:126-132
  • Evaluation of Renovascular Hypertension Captopril Renal Scan (ACEI Renography)
  • Captopril Renal Scan (ACEI Renography) Renovascular Disease  Renal artery stenosis (RAS)  Ischemic nephropathy  Renovascular hypertension (RVH) RAS ≠ RVH
  • Renin-Angiotensin System RAS Angiotensinogen Renin Angiotensin I Captopril ACE Angiotensin II Aldosterone Vasoconstriction HTN
  • Effect of RAS on GFR
  • Renovascular Hypertension  Prevalence   <1% unselected population with HTN Clinical features  Abrupt onset HTN in child, adult < 30 or > 60y  Severe HTN resistant to medical Rx  Unexplained or post-ACEI impairment in ren fct  HTN + abdominal bruits If these present - moderate risk of RVH (20-30%)
  • Diagnosis of RAS  Gold standard: angiography  Initial non-invasive tests:    ACEI renography Duplex sonography Other tests:  MRA - insensitive for distal / segmental RAS  Renal vein renin levels
  • Captopril Renal ScanMAG 3  Tc 99m MAG 3 = gold standard  Stop ACE inhibitors 48 hrs prior and no solid food before 4 hrs  Before procedure, orally fluid – 10 ml/kg  Hydration continued i.v. 4ml/ min  Baseline BP & PR recorded→ captopril 50 mg
  •  Protocol: 1 day vs. 2 day test  1 day test: baseline scan (1-2 mCi) followed by post-Capto scan (8-10 mCi)  2 day test: post-Capto scan, only if abnormal >> baseline
  • Abnormal captopril Renography      Delayed time to maximal activity >11 minutes(normal -5min) Significant asymmetry of peak activity of each kidney Marked cortical retention of radionuclide A marked decrease in the GFR of the ipsilateral kidney. 20-minute counts /peak counts [N <0.3 ], 0.15 change is considered significant.
  • Captopril Renal ScanMAG 3 MAG3 RENOGRAM CAPTOPRIL RENOGRAM TIME/ACTIVITY CURVE
  • AFTER 48 HOURS MAG3 RENOGRAM CAPTOPRIL RENOGRAM TIME/ACTIVITY CURVE
  • AORTOGRAM
  • ACEI Renography   In normal renal function - sens/spec ~ 90% In poor renal function / ischemic nephropathy, ACEI renography often indeterminate >>> do MRA, Duplex US, angiogram
  • Renal Cortical Scintigraphy Indications  Determine involvement of upper tract (kidney) in acute UTI (acute pyelonephritis)  Detect cortical scarring (chronic pyelonephr.)  Follow-up post Rx
  • CONTD..     gold standard 99mTc DMSA The radiotracer is taken up only by functioning PCT mass Pyelonephritis impairs tubular uptake of radiotracer, these areas appear as unexposed or underexposed Persisting areas on follow up indicates irreversible renal damage or scarring.
  • Renal Cortical Scintigraphy Cold Defect  Acute or chronic PN  Cyst  Tumors  Infarct  Trauma (contusion, laceration,hematoma) Cortical defects are not always d/t infection & all DMSA defects are not necessarily scars. 
  • —2-year-old girl with fever. Lim R AJR 2009;192:1197-1208 ©2009 by American Roentgen Ray Society
  • Renal Cortical Scintigraphy Congenital Anomalies  Agenesis  Ectopy  Fusion (horseshoe, crossed fused ectopia)  Polycystic kidney  Multicystic dysplastic kidney  Pseudotumors (fetal lobulation, hypertrophic column of Bertin , lobar nephronia)
  • NORMAL DMSA SCAN
  • HORSE SHOE KIDNEY
  • Horseshoe kidney with normal function
  • RENAL AGENESIS
  • Patient with Recurrent UTI Tc99m-DMSA renal SPECT scintigraphy Ectopic left kidney with multiple scars
  • Renal Transplant Evaluation:      Anterior images are obtained. Normal perfusion study: radioactive bolus reaches the renal transplant simultaneously with iliac vessels. Max parenchymal phase :3-5 min Bladder activity appears : 4-8 min Up to 2 weeks after Tx, prominent visualisation of ureter due to edema at UV anastomotic site.
  • Renal Transplant Scintigraphy Transplant kidney is showing good perfusion, uptake and drainage of radiotracerNormal Study Tc99m-DTPA renal dynamic scintigraphy
  • POST OP 1 WEEK POST OP 2 WEEKS
  •  Acute Tubular Necrosis: Preserved or mildly reduced renal perfusion but diminished renal function and progressive cortical retention of tubular agents. Acute Rejection : Poor perfusion than function in early stage Renogram demonstrates a diminished nephrogram phase and delayed appearance of bladder activity.
  • Renal Transplant Scintigraphy Acute Tubular Necrosis Acute Rejection Tc99m-DTPA renal dynamic scintigraphy
  • Renal Transplant Scintigraphy Transplant kidney is showing poor perfusion, uptake and drainage of radiotracer- Chronic Rejection Tc99m-DTPA renal dynamic scintigraphy
  • Cyclosporin nephrotoxicity :  Scintigraphic appearance similar to ATN, with relative good transplant perfusion and poor tubular function.  Compared to ATN ,it occurs several weeks after transplatation.
  • Renal transplants scintigraphy Surgical complications Urinary leak-Initial photopenic defect accumulation of radiotracer with progressive Hematoma/ Abscess- Initial photopenic defect not changing with time. Lymphocele- Initial photopenic defect- equal to background activity in delayed images. Ureteral obstruction Arterial stenosis and hypertension
  • Renal Transplant Scintigraphy 10th Post operative day of renal transplant decreased urine output and pelvic collection Urinary leak
  • Renal Transplant Scintigraphy 2nd Post operative day of renal transplant Hematoma / abscess
  • Renal Transplant Scintigraphy 7th Post operative day of renal transplant c/o Increased serum creatinine and pelvic collection Lymphocele
  • Radionuclide Cystogram INDICATIONS  Assess effect of therapy / surgery  Screening of siblings of reflux pts  Evaluation of children with recurrent UTI (30-50% have VUR) PROs  More sensitive  100 times less radiation CONs  Inferior anatomic deleniation
  • Radionuclide Cystogram
  • Refrences     Oxford text book of clnilcal nephrology-3rd ed. Essentials of Nuclear Medicine Imaging – Mettler & Guiberteau Brenner and Rector’s The kidney– 9th ed. www.google.com