THE SIX WISEMEN OF HINDOOSTAN

THE SIX WISEMEN OF HINDOOSTANNuclear Medicine for Bio-

EngineeringUniversity of Pittsburgh

Anna K. Chacko MDProfessor of Radiology, UPMC

What you will learn today

• What is Nuclear Medicine• How does it differ from other

imaging modalities in Radiology• Looking at some organ systems

through “Nuclear Eyes”

Nuclear Medicine and its subsets

Two divisions of Nuclear Medicine. • Looking at organ systems through “Nuclear Eyes” • Nuclear Therapeutics - Targeting the disease with

radionuclides that are preferentially sequestered in pathologic tissue

On the Horizon - Soon to be revealed

Copyright © 2007 by the American Roentgen Ray Society

--38-year-old woman with severe acute respiratory syndromeNormal Chest Radiograph

Is this patient dead or alive??

Looking at Physiology/Pathophysiology

This is a 38 year old female who presented with shortness of breath. Her chest x-ray was normal. Her lung function was not !!- her lung scan revealed multiple emboli.

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What does Nuclear Imaging do??

It looks at Life or the lack thereof

Definition of LifeThe consensus is that life is a characteristic of organisms that exhibit all or most of the following

phenomena:[9][10]

1. Homeostasis: Regulation of the internal environment to maintain a constant state; for example, electrolyte concentration or sweating to reduce temperature.

2. Organization: Being structurally composed of one or more cells, which are the basic units of life.

3. Metabolism: Consumption of energy by converting chemicals and energy into cellular components (anabolism) and decomposing organic matter (catabolism). Living things require energy to maintain internal organization (homeostasis) and to produce the other phenomena associated with life.

4. Growth: Maintenance of a higher rate of synthesis than catabolism. A growing organism increases in size in all of its parts, rather than simply accumulating matter. The particular species begins to multiply and expand as the evolution continues to flourish.

5. Adaptation: The ability to change over a period of time in response to the environment. This ability is fundamental to the process of evolution and is determined by the organism's heredity as well as the composition of metabolized substances, and external factors present.

6. Response to stimuli: A response can take many forms, from the contraction of a unicellular organism to external chemicals, to complex reactions involving all the senses of higher animals. A response is often expressed by motion, for example, the leaves of a plant turning toward the sun (phototropism) and chemotaxis.

7. Reproduction: The ability to produce new organisms. Reproduction can be the division of one cell to form two new cells. Usually the term is applied to the production of a new individual (either asexually, from a single parent organism, or sexually, from at least two differing parent organisms), although strictly speaking it also describes the production of new cells in the process of growth.

Wikipedia

Definition of Life

The consensus is that life is a characteristic of organisms that exhibit all or most of the following phenomena:

1. Homeostasis 2. Organization: 3. Metabolism:.4. Growth: 5. Adaptation: 6. Response to stimuli:7. Reproduction

Imaging Modalities and What They Reflect

Anatomy Physiology Metabolism Molecular

CT

US

MRI

SPECT & PET

Modality Fusion and Advantages Conferred

Anatomy Physiology Metabolism Molecular

CT

US

MRI

SPECT & PET

PET-CT/SPECT-CT

Six wise men of Hindoostan

There were six men of Hindoostan,

to learning much inclined,Who went to see an elephant,though all of them were blind,That each by observationmight satisfy his mind.

The first approached the elephant,and happening to fallAgainst his broad and sturdy side,at once began to bawl,"This mystery of an elephantis very like a wall."



The second, feeling of the tusk,cried, "Ho, what have we here,So very round and smooth and sharp?To me 'tis mighty clear,This wonder of an elephantis very like a spear."

The third approached the elephant,and happening to takeThe squirming trunk within his hands,thus boldly up and spake,"I see," quoth he,"the elephant is very like a snake."

The fourth reached out an eager hand,and felt above the knee,"What this most wondrous beastis like is very plain" said he,"'Tis clear enough the elephantis very like a tree."

The fifth who chanced to touch the earsaid, "E'en the blindest manCan tell what this resembles most;deny the fact who can;This marvel of an elephantis very like a fan."

The sixth no sooner had begunabout the beast to grope,Than seizing on the swinging tailthat fell within his scope;"I see," said he, "the elephantis very like a rope.”

So six blind men of Hindoostandisputed loud and long,Each in his own opinionexceeding stiff and strong;Though each was partly in the right,they all were in the wrong!

Systemic Disease

MalignancyInfectionTraumaDegenerative

Disease

Malignancy









Infection

The whole body In-111 labeled WBC images demonstrate increased activity in the left knee. Bone marrow imaging is performed for comparison at the same time of the WBC's study to assess the distribution of normal marrow (although in this case it is known there is no marrow in the region of the resected bone). There is discordant uptake (increased indium-111 activity with no increase in sulfur colloid activity) in the distal portion of remaining left femur. This is consistent with osteomyelitis adjacent to the femoral prosthesis..





Bone Marrow Scan

The three major tissue that constitute the red marrow includethe hematopoietic (erythropoietic and myelopoietic) cells;the Reticuloendothelial cells; andthe trabecular framework, that supports both cell types. The RE cells generally parallel the blood forming cells. Therefore, the RE cell images gives an indication of the state of the bone marrow.



Head & Neck

Brain

Salivary Glands

Lacrimal Glands

Thyroid

Parathyroid

Brain Imaging

Glucose powers the brain, and evidence indicates that a progressively diminishing capacity to make use of glucose - contributing to the dysfunction which is Alzheimer’s disease. The imaging technique uses 18FDG for evaluating the disease.



Brain Imaging

An HIV positive patient's brain showing abnormal uptake of fluorodeoxyglucose labeled with 18FDG in the left parietal region. MRI showed a lesion at this site, but could not distinguish between toxoplasmosis and lymphoma, both of which may present in HIV positive patients. Uptake indicates that the patient has a lymphoma--Toxoplasmosis has no uptake of fluorodeoxyglucose



Brain Imaging - Iodine-123 dopamine transporter ligand

Images from nuclear medicine can help in diseases such as suspected Parkinson's disease, where the dopamine transporters are diminished in the basal ganglia. Imaging these gives an indication of the degree of severity of the disease. The test uses a dopamine transporter ligand labeled with iodine-123, which shows where the dopamine transporters are situated.



Uptake of ioflupane, a cocaine analogue, labeled with 123I,which binds to sites of dopamine transporters in the basal ganglia.Uptake occurs in the caudate nuclei but not in the putamen, which is typicalof Parkinson's disease.

Brain Death







Thyroid Hormone

The iodide cycle

Ingested iodide is trapped in the thyroid, oxidized, and bound to tyrosine to form iodotyrosines in Thyroglobulin (TG); coupling of iodotyrosyl residues forms T4 and T3. Hormone secreted by the gland is transported in serum. Some T4 is deiodinated to T3. The hormone exerts its metabolic effect on the cell and is ultimately deiodinated; the iodide is reused or excreted in the kidney. A second cycle goes on inside the thyroid gland, with deiodination of iodotyrosines generating iodide, some of which is reused without leaving the thyroid.





Thyroid Cancer

Well-differentiated thyroid cancer metastatic to the lungs.

Iodine 131 scan used for surveillance

Thyroid disease







Normal thyroid Multi nodular goiter



Multi nodular goiter Sublingual thyroid

Parathyroid Imaging Parathyroid glands are responsible

for Calcium and phosphorus homeostasis.This is done through the production of parathyroid hormone

Adenomas of the parathyroid glands are known to produce problems with the Ca++ balance in the body. These when associated with hyperparathyroidism can lead to loss of bone mineral (Osteoporosis) among other symptoms.



The Thorax

Cardiac Imaging

Pulmonary (Lung) Imaging

Lung Scan

The lung receives venous (deoxygenated blood) from the body and facilitates the exchange of Oxygen for Carbon Dioxide. With lung scans these two functions - perfusion and ventilation are evaluated



Myocardial Scan

Various types of studies can be performed to assess the function and the viability of the myocardium (Heart Muscle). In the MPI study, the state of the myocardium at rest is compared with the state under stress. If a “reversible” defect is identified, the patient is likely to benefit from intervention (stenting or CABG)





Recent article

March 2, 2010

Radiology in Practice

Will CT overtake nuclear medicine in myocardial perfusion?

It's not enough that sidelined nuclear reactors are restricting the supply of technetium for cardiac SPECT. Or that reimbursements for SPECT procedures are falling. Now the besieged modality has to contend with

a challenge from CT.



Liver - Spleen

Gall Bladder

Bowel

Stomach

Kidneys and the Genitourinary tract

Adrenals

Prostate

Testes

Testicular Scan - TORSION

The testes are suspended in the scrotum by a single bundle of tissues that also carries the blood supply to and from the testes. If the testicle rotates, the bundle kinks, and the blood supply is shut off. The resulting situation is an emergency because the testis will die within hours if the blood supply is not restored.


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Testicular Scan - INFECTION

On physical examination, it is difficult to distinguish testis from epididymis because of localized swelling. For this reason the condition is frequently misdiagnosed as epididymis. Therefore, imaging of the scrotum is very important for the diagnosis of the specific etiology of the patients presenting with acute scrotum. Prompt differential diagnosis should be made between acute testicular torsion and acute infections of testis and epididimytis, since torsion of the testicle is a true surgical emergency of the highest order.

Prostate CancerWhole Body ProstaScint Scan of a Patient with Rising PSA while Undergoing Hormonal Therapy. ProstaScint activity in a left supraclavicular lymph node and in many central abdominal lymph nodes (arrows) indicates a high likelihood of metastatic disease and hormone resistant tumor.ProstaScint is a radioimmunoconjugate of a monoclonal antibody directed against Prostate Specific Membrane Antigen, expressed in malignant prostatic tissue



Gall Bladder Scan

The agent used for scanning the gall bladder follows a path similar to the production and distribution of Bile. = Iminodiacetic acid. The function of the gallbladder is assessed by evaluating the GB Ejection Fraction after administering a drug which should make the gallbladder contract.

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GI bleeding Study The agent used for

Gastrointestinal bleeding is Red Blood cells labeled with Tc 99mO4. = Normally the bowel should not show any tracer. When this shows up - the site of the GI bleeding has been discovered.



Renal Scan

Kidneys are one of a set several organs that maintain blood pressure (BPr). When a patient presents with High BPr, the kidneys are investigated. When the blood supply to the kidney is compromised, it responds by raising BPr. The kidney’s integrity is studied by using nuclear medicine following administration of a drug that provokes a response from a compromised kidney.





Normal Captopril study

Liver-Spleen Scan

The liver, spleen, bone marrow and to some extent the lungs are the repository of Reticuloendothelial cells which serve as “police” functioning to get rid of harmful agents in the body. These cells are called Kupffer cells. Colloidal sulfur particles labeled with Tc 99m are injected i.v. These particles are ingested by the RE cells and images of the organs are produced



Meta-iodo-benzyl guanidineSince MIBG structurally resembles norepinephrine, it enters neuroendocrine cells by an active uptake mechanism and is stored in the neurosecretory granules, resulting in a specific concentration in contrast to cells of other tissues. MIBG scintigraphy is used to image tumours of neuroendocrine origin, particularly those of the sympathoadrenal system (phaeochromocytomas, paragangliomas and neuroblastomas), although other neuroendocrine tumours (carcinoids, medullary thyroid carcinoma, etc.) are also visualized.

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Meta-iodo-benzyl guanidine



Patient with medullary thyroid cancer with positive MIBG scan

In111 pentetreotide

Indium-111 Pentetreotide is a cyclic octapeptide analog of somatostatin. DTPA allows labeling with In-111. Excreted primarily by the renal system. In-111 pentetreotide imaging is a sensitive method for detecting presence of tumors such as glucagonomas, vipomas, carcinoids, nonfunctioning islet cell tumors.





TheragnosticsPene F, Courtine E, Cariou A, Mira JP. Crit Care Med. 2009 Jan;37(1 Suppl):S50-8.Theragnostics is a treatment strategy that combines therapeutics with diagnostics. It associates

both a diagnostic test that identifies patients most likely to be helped or harmed by a new medication, and targeted drug therapy based on the test results. Bioinformatics, genomics, proteomics, and functional genomics are molecular biology tools essential for the progress of molecular Theragnostics. These tools generate the genetic and protein information required for the development of diagnostic assays. Theragnostics includes a wide range of subjects, including personalized medicine, pharmacogenomics, and molecular imaging to develop efficient new targeted therapies with adequate benefit/risk to patients and a better molecular understanding of how to optimize drug selection. Furthermore, Theragnostics aims to monitor the response to the treatment, to increase drug efficacy and safety. In addition, Theragnostics could eliminate the unnecessary treatment of patients for whom therapy is not appropriate, resulting in significant drug cost savings for the healthcare system. However, the introduction of Theragnostics tests into routine health care requires both a demonstration of cost-effectiveness and the availability of appropriate accessible testing systems. This review reports validation studies in oncology and infectious diseases that have demonstrated the benefits of such approach in well-defined subpopulations of patients, moving the field from the drug development process toward clinical practice and routine application. Theragnostics may change the usual business model of pharmaceutical companies from the classic blockbuster model toward targeted therapies.

Six wise men of Hindoostan

There were six men of Hindoostan,to learning much inclined,Who went to see an elephant,though all of them were blind,That each by observationmight satisfy his mind.

The first approached the elephant,and happening to fallAgainst his broad and sturdy side,at once began to bawl,"This mystery of an elephantis very like a wall."



The second, feeling of the tusk,cried, "Ho, what have we here,So very round and smooth and sharp?To me 'tis mighty clear,This wonder of an elephantis very like a spear."

The third approached the elephant,and happening to takeThe squirming trunk within his hands,thus boldly up and spake,"I see," quoth he,"the elephant is very like a snake."

The fourth reached out an eager hand,and felt above the knee,"What this most wondrous beastis like is very plain" said he,"'Tis clear enough the elephantis very like a tree."

The fifth who chanced to touch the earsaid, "E'en the blindest manCan tell what this resembles most;deny the fact who can;This marvel of an elephantis very like a fan."

The sixth no sooner had begunabout the beast to grope,Than seizing on the swinging tailthat fell within his scope;"I see," said he, "the elephantis very like a rope.”

So six blind men of Hindoostandisputed loud and long,Each in his own opinionexceeding stiff and strong;Though each was partly in the right,they all were in the wrong!

WHAT’S NEW ON THE HORZON!?!

• Theragnostics• Compressive/compressed sensing - allowing the

construction of large and accurate/fine resolution/great replicability data sets from SPARSE ones.

• Increasing concerns over radiation burden through medical procedures

• The use of Thorium reactors - unlimited supplies of energy.

WHAT DOES THIS MEAN FOR US - TRUE HEALTHCARE REFORM. - A BRAVE NEW FUTURE FOR THE YOUNGER GENERATIONS OR THE GENERATIONS AS YET UNBORN.

Health & Medicine

THE SIX WISEMEN OF HINDOOSTAN