9.2 Central Nervous System Imaging

Central Nervous System (CNS) nuclear medicine provides unique functional insights that anatomical imaging (CT/MRI) often cannot match. By visualizing regional cerebral blood flow (rCBF), neurotransmitter density, and cerebrospinal fluid (CSF) dynamics, nuclear medicine plays a pivotal role in diagnosing complex neurological disorders ranging from dementias and movement disorders to intractable epilepsy.

Brain Perfusion SPECT Imaging

Regional cerebral blood flow is tightly coupled to neuronal metabolism; active brain regions require more blood. By mapping blood flow, we indirectly map brain function.

Radiopharmaceuticals: Crossing the Barrier

The brain is protected by the blood-brain barrier (BBB), which prevents most large or hydrophilic molecules from entering the cerebral cortex. To image brain perfusion, radiopharmaceuticals must be lipophilic (lipid-soluble) and neutrally charged to cross the intact BBB. Once inside the brain cells, they are converted into hydrophilic compounds, effectively trapping them in place. The two primary agents used are:

1. Tc-99m HMPAO (Ceretec, exametazime): Highly lipophilic, crosses the BBB rapidly. Its distribution is proportional to blood flow. A critical technical detail: HMPAO is inherently unstable and must be used within 30 minutes of preparation, or stabilized (typically with cobalt or methylene blue) to extend its shelf life to 4-6 hours.
2. Tc-99m ECD (Neurolite, bicisate): Also lipophilic and crosses the BBB. It is more stable in vitro than unstabilized HMPAO and demonstrates faster blood clearance, resulting in a higher target-to-background ratio and arguably superior image quality.

Patient Preparation and Injection Protocol

The environment at the time of injection permanently sets the radiotracer distribution. Therefore, meticulous preparation is required to establish a true baseline:

• An intravenous (IV) line should be placed 10-15 minutes prior to injection to avoid pain-induced perfusion changes.
• The patient must rest in a quiet, dimly lit room with their eyes open or closed (depending on institutional protocol) but undirected, with minimal sensory stimulation.
• The technologist injects the tracer (typically 20-30 mCi) through the IV without speaking to or disturbing the patient.
• Imaging can commence 30-90 minutes post-injection, as the tracer remains fixed in the brain. The scan requires a multi-detector gamma camera equipped with high-resolution or ultra-high-resolution collimators, stepping 360 degrees around the patient's head, typically using a 128x128 matrix.

Clinical Applications of Perfusion SPECT

• Stroke (Cerebrovascular Accident): While CT/MRI are frontline, SPECT can detect acute ischemia earlier than CT as a cold defect. More importantly, it can identify the penumbra—tissue that is ischemic but potentially salvageable.
• Dementia Evaluation: Different dementias have signature perfusion deficits. Alzheimer's disease typically shows bilateral temporoparietal hypoperfusion. Frontotemporal dementia (Pick's disease) shows, as the name implies, hypoperfusion in the frontal and temporal lobes.

Epilepsy Imaging: Ictal vs. Interictal SPECT

For patients with medically refractory epilepsy, surgical resection of the seizure focus is a viable treatment. Accurate localization of this focus is paramount.

• Interictal SPECT (Between Seizures): When the patient is not seizing, the epileptogenic focus is typically hypometabolic and receives less blood flow. The scan will demonstrate a focal area of hypoperfusion (a 'cold spot').
• Ictal SPECT (During a Seizure): This requires the patient to be monitored in an epilepsy monitoring unit (EMU) with continuous EEG and an established IV line. At the onset of a seizure, the technologist or nurse immediately injects the tracer. During a seizure, the epileptogenic focus becomes hypermetabolic. The scan will demonstrate a focal area of intense hyperperfusion (a 'hot spot'). By co-registering the ictal SPECT, interictal SPECT, and MRI (SISCOM technique), neurosurgeons obtain highly accurate localization for surgical planning.

Dopamine Transporter Imaging (DaTscan)

Movement disorders often present diagnostic challenges clinically. DaTscan is a specialized SPECT study used to differentiate Essential Tremor from Parkinsonian syndromes (including idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy).

The Radiopharmaceutical: I-123 Ioflupane

I-123 ioflupane binds specifically to presynaptic dopamine transporters (DaT) located on the terminals of dopaminergic neurons projecting from the substantia nigra to the striatum (caudate nucleus and putamen). Because it contains iodine, patients must receive a blocking agent (e.g., SSKI, Lugol's solution, or potassium perchlorate) at least 1 hour prior to injection to protect the thyroid gland from free radioactive iodine.

Image Interpretation and Anatomy

• Normal Pattern: A healthy striatum exhibits robust DaT activity in both the anterior caudate and the posterior putamen. Bilaterally, this appears as two bright, symmetric, comma-shaped or crescent-shaped areas.
• Abnormal Pattern (Parkinsonian Syndrome): As dopaminergic neurons degenerate, DaT density decreases. The loss typically begins asymmetrically in the posterior putamen and progresses anteriorly. On the scan, the "tail" of the comma disappears, leaving only uptake in the anterior caudate. The commas become "periods" or "dots." This confirms a nigrostriatal degenerative disease.
• Essential Tremor: In patients with essential tremor, the dopaminergic pathways are entirely intact. Therefore, a DaTscan in these patients will be entirely normal (comma-shaped).

Cerebrospinal Fluid (CSF) Cisternography

Cisternography evaluates the flow, dynamics, and reabsorption of cerebrospinal fluid. The procedure involves a physician performing a lumbar puncture to inject the radiotracer directly into the subarachnoid space (intrathecally).

Radiopharmaceutical: In-111 DTPA

Indium-111 DTPA is the agent of choice due to its physical half-life of 2.8 days, which allows for delayed imaging up to 48 or 72 hours. It emits 171 and 247 keV gamma rays.

Normal Pressure Hydrocephalus (NPH)

NPH is a treatable cause of dementia characterized by the clinical triad of gait disturbance, urinary incontinence, and cognitive decline. It is caused by impaired CSF reabsorption at the arachnoid villi.

• Normal Pattern: Tracer ascends the spinal canal, reaches the basal cisterns by 2-4 hours, flows over the cerebral convexities by 24 hours, and clears into the sagittal sinus. It does not enter the lateral ventricles.
• NPH Pattern: Because reabsorption over the convexities is blocked, the CSF is forced backwards. The tracer demonstrates early and persistent ventricular reflux (entering the lateral ventricles, creating a "heart-shaped" appearance) and a significant delay or failure of ascent over the cerebral convexities at 24, 48, and sometimes 72 hours. This finding suggests the patient may benefit from a ventricular shunt.

CSF Leak Detection

Cisternography is also used to detect CSF leaks (otorrhea or rhinorrhea) following trauma or surgery. Small cotton pledgets are placed in the patient's nose or ears prior to injection. After several hours, the pledgets are removed, placed in individual tubes, and counted in a well counter. If the counts in a pledget significantly exceed the patient's blood background activity, a CSF leak is confirmed.