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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
Technetium99m

 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 two-
dimensional 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
Grouped into three categories:
1. 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

51Cr-EDTA

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
• 99mTc-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

-C-NH-CH2-COOH

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.
 123I-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 coo-
Tc
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)

HS COOH

HS COOH

H
Cortical agents
 Tc99m DMSA-
PYELONEPHRITIS, 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 O
O
C Tc C

CH CH
O O
(CHOH)4 (CHOH)4

CH2OH 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 Agent


Perfusion MAG3, DTPA, GHA
Morphology DMSA, GHA
Obstruction MAG3, DTPA, OIH
GFR quantitation I-125 iothalamate,
Cr-51 EDTA, DTPA
ERPF quantitation 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  FUNCTIONAL PHASE (
(RADIONUCLETIDE 30 MIN )
ANGIOGRAM) 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


SPLIT FUNCTION
after peak aortic activity
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
net cts in Lt ROI
% Lt kid = --------------------------------------- x 100%
net cts Lt + net cts Rt ROI

ROI: Region of interest


Normal 50/50 - 56/44
Borderline 57/43 - 59/41
Abnormal > 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
CAPTOPRIL RENOGRAM
MAG3 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 radiotracer-
Normal 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 with progressive
accumulation of radiotracer
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 PROs
 Assess effect of therapy  More sensitive

/ surgery  100 times less radiation

 Screening of siblings of CONs


reflux pts  Inferior anatomic

 Evaluation of children
deleniation
with recurrent UTI
(30-50% have VUR)
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